Recasting Human Vδ1 Lymphocytes in an Adaptive Role

Vδ1 T cells are the predominant tissue-associated γδ T cell subset in humans, and can recognise signs of cellular dysregulation, including viral infection and transformation. They are often assumed to be innate-like effectors. The Vδ1 TCR repertoire is initially diverse, yet a few clonotypes typically expand heavily over time. Such expanded clonotypes are diverse in sequence both within and between individuals. Clonal expansion occurs concurrently with differentiation from Vδ1 Tnaïve to Vδ1 Teffector status, alongside a switch from lymphoid to peripheral homing receptors, and upregulation of cytotoxic pathways. This concurrent expansion and differentiation suggests an adaptive-like response, likely driven by diverse stimuli, including microbial pathogen infection. γδ T cells are unconventional lymphocytes commonly described as ‘innate-like’ in function, which can respond in both a T cell receptor (TCR)-independent and also major histocompatibility complex (MHC)-unrestricted TCR-dependent manner. While the relative importance of TCR recognition had remained unclear, recent studies revealed that human Vδ1 T cells display unexpected parallels with adaptive αβ T cells. Vδ1 T cells undergo profound and highly focussed clonal expansion from an initially diverse and private TCR repertoire, most likely in response to specific immune challenges. Concomitantly, they differentiate from a Vδ1 T cell naïve (Tnaïve) to a Vδ1 T cell effector (Teffector) phenotype, marked by the downregulation of lymphoid homing receptors and upregulation of peripheral homing receptors and effector markers. This suggests that an adaptive paradigm applies to Vδ1 T cells, likely involving TCR-dependent but MHC-unrestricted responses to microbial and non-microbial challenges. γδ T cells are unconventional lymphocytes commonly described as ‘innate-like’ in function, which can respond in both a T cell receptor (TCR)-independent and also major histocompatibility complex (MHC)-unrestricted TCR-dependent manner. While the relative importance of TCR recognition had remained unclear, recent studies revealed that human Vδ1 T cells display unexpected parallels with adaptive αβ T cells. Vδ1 T cells undergo profound and highly focussed clonal expansion from an initially diverse and private TCR repertoire, most likely in response to specific immune challenges. Concomitantly, they differentiate from a Vδ1 T cell naïve (Tnaïve) to a Vδ1 T cell effector (Teffector) phenotype, marked by the downregulation of lymphoid homing receptors and upregulation of peripheral homing receptors and effector markers. This suggests that an adaptive paradigm applies to Vδ1 T cells, likely involving TCR-dependent but MHC-unrestricted responses to microbial and non-microbial challenges. γδ T cells have coevolved alongside αβ T cells and B cells for at least the past ∼450 million years of vertebrate evolution 1Hayday A.C. γδ cells: a right time and a right place for a conserved third way of protection.Annu. Rev. Immunol. 2000; 18: 975-1026Crossref PubMed Scopus (956) Google Scholar, 2Hirano M. et al.Evolutionary implications of a third lymphocyte lineage in lampreys.Nature. 2013; 501: 435-438Crossref PubMed Scopus (160) Google Scholar, each distinguished by related but distinct somatically recombined antigen receptors. However, our understanding of these different lineages is strikingly imbalanced. Critical to our understanding of αβ T cell and B cells is the classical adaptive paradigm (Box 1). Within this, seminal discoveries have established the core function of the αβ T cell lineage: to enable immune responses to target cells based on the presence on their surface of antigenic peptide in the context of MHC molecules; similarly, we understand that B cells, which underpin humoral immunity, enable the production of soluble of a diverse of antigenic in with that is in the and clonal of adaptive lymphocytes of of production the of clonal Scholar], studies have both the of in αβ and B cell receptor and the of in of their (Box of αβ T cells and B cells of classical adaptive of a and αβ T cell and B cell lineages somatically recombined and with in their both lymphocyte are for immune αβ T cells undergo and in the B cells, in the undergo both based on and that including and from a of clonotypes from within the diverse naïve immune receptor repertoire expansion of specific αβ T cell and B cell clonotypes receptors that enable responses to specific immune as pathogen with clonal both αβ T cell and B cell lineages undergo differentiation to but also the of expanded and immune responses are in response to antigenic of studies the for and in αβ T cell and B cell clonal and and the that is a of adaptive lymphocyte αβ T cells and B cells of classical adaptive of a and αβ T cell and B cell lineages somatically recombined and with in their both lymphocyte are for immune αβ T cells undergo and in the B cells, in the undergo both based on and that including and Clonal from a The of clonotypes from within the diverse naïve immune receptor repertoire expansion of specific αβ T cell and B cell clonotypes receptors that enable responses to specific immune as pathogen infection. with clonal both αβ T cell and B cell lineages undergo differentiation to but also the of expanded and immune responses are in response to antigenic Critical of studies the for and in αβ T cell and B cell clonal and and the that is a of adaptive lymphocyte studies αβ TCR et receptor within the and in PubMed Scopus Google Scholar, et third and in a of cytotoxic T PubMed Scopus Google γδ T cells have by remained both in of the they and the for their as a third lymphocyte lineage within vertebrate γδ T cells are in a of immune including immunity, immunity, and in of T cells to Rev. Immunol. 2013; PubMed Scopus Google the that their and antigen recognition are a of the related of the importance and of γδ TCR in γδ T cell a from studies of γδ T cells is that γδ T cell of adaptive as ‘innate-like’ γδ T cells distinct and at different and often display TCR in highly et antigen receptor of of T PubMed Scopus Google Scholar, et of antigen receptor of PubMed Scopus Google Scholar, et of a subset with receptors to PubMed Scopus Google They can be to differentiate effector et T cell effector cells and cells PubMed Scopus Google Scholar, A.C. a for the of T PubMed Scopus Google lymphocyte have to be in on the of et to T cell PubMed Scopus Google Such of unconventional lymphocytes are to be of to target cells the for clonal expansion and with the recognise a of et and function of T cells PubMed Scopus Google Scholar], and that their recognition receptors for of humans, the γδ T cell subset that most to is by a and the predominant peripheral subset of T et by for the presence of the major of human peripheral T PubMed Scopus Google on their TCR and and presence of production of and to and of recognition on the subset to an innate-like the recognition of target cells the of these γδ T cell of unconventional αβ T cell T cells and cells which also highly TCR et T cell receptor is in by expanded T PubMed Scopus Google Scholar, et T cell receptor a major histocompatibility complex T cell in PubMed Scopus Google Scholar], and have to recognise and of differentiation to the of the lymphoid A.C. T cells and the lymphoid PubMed Scopus Google Scholar], which that by the for clonal and from microbial non-microbial the of the response, adaptive immune responses have in that can be their but also by T cells a subset of γδ T cells in can be receptor recognition of on of the TCR et upregulation of an of a immune with on Immunol. PubMed Scopus Google human T cells TCR-dependent recognition of target cells, they can also be by and are to as et the response of human T cells to of microbial Immunol. Google Scholar, et production from cells and T cells in human Immunol. Google Scholar, et of T cells by Immunol. PubMed Scopus Google recent studies on and γδ T cell that TCR with are for the and of their effector A.C. a for the of T PubMed Scopus Google Scholar, et to T cell PubMed Scopus Google these cells can to TCR and function in an to respond to signs of cellular M. et T cells and adaptive by Immunol. PubMed Scopus Google to T cells, a human γδ T cell of which the Vδ1 is Vδ1 T cells are the most of γδ T cells at et and of human T cells at Immunol. Google Scholar], and the γδ T cell in peripheral in as the et major of human lymphocytes the T cell the and the Immunol. PubMed Scopus Google Scholar, et T cells of the and are in Immunol. PubMed Scopus Google and et receptor cells in human PubMed Scopus Google Vδ1 T cells have remained an in of the their on their predominant effector phenotype, their with their to recognise both and also cells, and their of et of T cells cells and PubMed Scopus Google Scholar, et of MHC receptors to a expansion of T Immunol. PubMed Scopus Google Scholar, et expansion of T cells is a specific of PubMed Scopus Google Scholar], they have often assumed to in an innate-like to cells, recognition of diverse cellular in target cells. However, we recent that have and that Vδ1 T cells a adaptive of the most in γδ T cell including the importance and of the γδ TCR that the but is The of of the repertoire within the αβ and B cell et of in and 2013; PubMed Scopus Google Scholar, for receptor repertoire PubMed Scopus Google of these to human peripheral γδ T cells on clonal evolution within the γδ T cell The with the the to γδ T cells from αβ to of recombined in αβ T cells et of the human and suggests that and T cell PubMed Scopus Google of these is the for and sequence et of the receptor and Scopus Google the of in and can in of often from of be highly TCR The of to the of TCR et for receptor 2013; PubMed Scopus Google Scholar], et for adaptive PubMed Scopus Google Scholar], and et an for T cell receptor repertoire PubMed Scopus Google which challenges. are to based on the of between cells in different differentiation as TCR be to TCR with cell on a specific et and of and receptor from PubMed Scopus Google Scholar, et in the human T cell repertoire TCR-dependent adaptive immune PubMed Scopus Google Scholar, et T cells are and adaptive clonal expansion in response to viral Immunol. 18: PubMed Scopus Google Such studies have on Vδ1 T cell but have also of the Vδ1 repertoire that with that of both peripheral T cells and γδ T cells. based on of the Vδ1 TCR repertoire at the of which a of is diverse, a of in these are in that clonotypes are with sequence of the repertoire 1). This with the in and clonotypes that are at the between and are with of a repertoire in for recognition et of the human and suggests that and T cell PubMed Scopus Google Scholar, et of and on T Immunol. PubMed Scopus Google Scholar, et T cells the response to 2013; PubMed Scopus Google Scholar, et T cells the human PubMed Scopus Google from studies is in to Vδ1 are in typically from the presence of a of heavily expanded and which often for a of the Vδ1 TCR by et et in the human T cell repertoire TCR-dependent adaptive immune PubMed Scopus Google and et et T cells are and adaptive clonal expansion in response to viral Immunol. 18: PubMed Scopus Google to that these clonal and by both and TCR private to an at both a and et in the human T cell repertoire TCR-dependent adaptive immune PubMed Scopus Google with the of expanded clonotypes highly diverse, and their both within and between et in the human T cell repertoire TCR-dependent adaptive immune PubMed Scopus Google to from the of of by of for Vδ1 the private of the Vδ1 repertoire and the presence of clonal with the TCR repertoire, which and in and et of the human and suggests that and T cell PubMed Scopus Google Scholar, et in the human T cell repertoire TCR-dependent adaptive immune PubMed Scopus Google Scholar, et T cells the response to 2013; PubMed Scopus Google with Vδ1 T cells, the T cell repertoire and with also display which is likely by the of recognition et in immune PubMed Scopus Google γδ TCR repertoire have also clonal et that infection cell can expansion of TCR clonotypes et T cells are and adaptive clonal expansion in response to viral Immunol. 18: PubMed Scopus Google also to be on studies the importance of T cells in responses to infection and in et expansion of T cells is a specific of PubMed Scopus Google Scholar, et of T cells in the human immune response to PubMed Scopus Google Scholar, et infection in T lymphocytes a PubMed Scopus Google Scholar], including with a of in et expansion of T cells is a specific of PubMed Scopus Google this, the to infection is both et et T cells are and adaptive clonal expansion in response to viral Immunol. 18: PubMed Scopus Google and et et in the human T cell repertoire TCR-dependent adaptive immune PubMed Scopus Google that the Vδ1 repertoire of clonal that TCR clonal expansion an of infection 1). The for is unclear, but different of of the response on γδ T cells, the presence of in the Vδ1 TCR repertoire in individuals. studies are to these also had heavily expanded Vδ1 that infection is the immune that Vδ1 T cell responses 1). with diverse for the Vδ1 expansion of Vδ1 T cells also in response to et cell receptor lymphocyte Immunol. Google and in in et of T cells by T cells in PubMed Scopus Google Scholar], Vδ1 clonal infection in et T cells in 2013; PubMed Scopus Google Scholar, et T cell receptor repertoire of T lymphocytes human cell and the for B cells in clonal Immunol. PubMed Scopus Google in to be of the both et et in the human T cell repertoire TCR-dependent adaptive immune PubMed Scopus Google and et et T cells are and adaptive clonal expansion in response to viral Immunol. 18: PubMed Scopus Google that expanded clonotypes can be and for at least with to et et in the human T cell repertoire TCR-dependent adaptive immune PubMed Scopus Google TCR TCR and a to different Vδ1 in peripheral and a Vδ1 subset highly diverse and to naïve T cells, including and we the to Tnaïve cells typically a of peripheral Vδ1 T cells, the Vδ1 T cell subset in expanded Vδ1 in within a effector in which to different within peripheral Vδ1 T cells a This with Teffector including of and receptor we the to the that the Vδ1 of the of diverse Vδ1 TCR by Vδ1 Tnaïve cells the of and that clonal expansion and differentiation of Vδ1 T cell of Vδ1 Tnaïve and Teffector an adaptive the from Vδ1 Tnaïve to Teffector subset is by a of homing receptor Vδ1 Tnaïve cells of lymphoid homing markers. Vδ1 Teffector cells downregulation of and but which to an homing The of these on Vδ1 Tnaïve and Teffector on naïve and cell and as for Teffector cells et receptor T with distinct in immune and PubMed Scopus Google Scholar], Vδ1 Teffector cells be in of function, Vδ1 Tnaïve cells, as naïve T cells, of cytotoxic effector and and these heavily in Vδ1 Teffector cells to Vδ1 Teffector cells a and TCR and to relative to Vδ1 Tnaïve cells, which to naïve T to and TCR that the and highly TCR focussed naïve and effector Vδ1 and from a effector subset from Vδ1 T cells are initially highly naïve in and an TCR They also that differentiation to an effector is an but is to clonal and both cytotoxic and homing receptor The parallels between Vδ1 T cells and classical adaptive T cell T they between Vδ1 T cells and the T cell They that the γδ TCR is to the of Vδ1 T cells, and to a of MHC-unrestricted adaptive applies to the Vδ1 T cell subset (Box This paradigm and the that implications of that likely of that of an adaptive to Vδ1 T cells. specific stimuli, including microbial infection are of the clonal expansion and differentiation of Vδ1 Teffector clonotypes from a highly diverse, Vδ1 Tnaïve as for αβ T cells and B cells, in context the of the Vδ1 γδ TCR to clonal expansion and differentiation to the effector expanded Vδ1 Teffector which are immune challenges. that of an adaptive to Vδ1 T cells. specific stimuli, including microbial infection are of the clonal expansion and differentiation of Vδ1 Teffector clonotypes from a highly diverse, Vδ1 Tnaïve as for αβ T cells and B cells, in context the of the Vδ1 γδ TCR to clonal expansion and differentiation to the effector and expanded Vδ1 Teffector which are immune challenges. The Vδ1 and T cell at different with a distinct and TCR repertoire for the T cells are in the and the and are in in the of human T cells Immunol. Google Scholar, et and of T cell receptor in human PubMed Scopus Google for as and expansion microbial et for in the T cell receptor PubMed Scopus Google Vδ1 T cells are the γδ T cell in the is human γδ T cells undergo The of and for Vδ1 and TCR a for is of in γδ T cells et of the human and suggests that and T cell PubMed Scopus Google peripheral be in the of cells, to in et of cells to Immunol. PubMed Scopus Google be to for Vδ1 γδ T cells as which be in et of MHC receptors to a expansion of T Immunol. PubMed Scopus Google TCR and to to TCR et and by of a human T cell antigen receptor to Immunol. PubMed Scopus Google the cellular of Vδ1 clonal are unclear, the immune of Vδ1 Tnaïve cells suggests to lymphoid as to expanded Vδ1 Teffector This that Vδ1 Tnaïve cells most likely between and and suggests that clonal lymphoid is a in lymphoid studies the differentiation and of Vδ1 T cells in lymphoid be to these and on specific cell are in the of on Vδ1 Teffector and their to suggests that they to and to a focussed repertoire at studies the and TCR of peripheral Vδ1 T cells with in these the by the γδ TCR a major and that the by which γδ T cells recognise target cells TCR in the of receptor receptor peripheral and of T γδ TCR of T of T of of T from with of T cells in private likely γδ Teffector for cells of on on et of T cells cells and PubMed Scopus Google Scholar, et of MHC receptors to a expansion of T Immunol. PubMed Scopus Google Scholar, et and by of a human T cell antigen receptor to Immunol. PubMed Scopus Google Scholar, et receptor is in as a of and of PubMed Scopus Google Scholar, et of the cell receptor in PubMed Scopus Google of of T TCR γδ clonotypes in Vδ1 T to γδ Teffector from of T cells to recognise of on γδ T cells and to et T cells a microbial B cell antigen to a PubMed Scopus Google with of of T clonotypes in Vδ1 T to γδ T cells expand recognition of et antigen recognition by the Immunol. 2013; PubMed Scopus Google Scholar, et of T cells in human a Immunol. PubMed Scopus Google Scholar, et of T cell receptor in complex with recognition of a by human T 2013; PubMed Scopus Google with of of T clonotypes in Vδ1 T to γδ Teffector γδ Tnaïve γδ T cells expand recognition of et of T cells by Immunol. PubMed Scopus Google with clonotypes of in in cellular γδ T cells to recognise cells et of cell by human TCR-dependent recognition of PubMed Scopus Google receptor receptor peripheral and of T in a γδ TCR have focussed on peripheral our understanding of the Vδ1 TCR repertoire in is However, a recent a at in in different which TCR-dependent in response to target cells et to T cell PubMed Scopus Google for is to understand as for and the TCR repertoire and of cells a innate-like paradigm an adaptive a understanding of the Vδ1 TCR repertoire in different is on peripheral Vδ1 T cells a highly diverse TCR repertoire both in of and are in the of Vδ1 in of these to et in the human T cell repertoire TCR-dependent adaptive immune PubMed Scopus Google The of within the Vδ1 TCR repertoire, including of diverse with unconventional T cell to recognise et T cell receptor is in by expanded T PubMed Scopus Google Scholar], et T cell receptor a major histocompatibility complex T cell in PubMed Scopus Google Scholar], and T cells et in the human T cell repertoire TCR-dependent adaptive immune PubMed Scopus Google Scholar, et T cells are and adaptive clonal expansion in response to viral Immunol. 18: PubMed Scopus Google which TCR including by the Vδ1 TCR repertoire is both diverse and private et in the human T cell repertoire TCR-dependent adaptive immune PubMed Scopus Google Scholar, et T cells are and adaptive clonal expansion in response to viral Immunol. 18: PubMed Scopus Google the of the peripheral Vδ1 TCR repertoire, including in expanded recognition of a of between individuals. is for in αβ TCR the complex can be by of diverse sequence et human T cell receptors in a to the peptide complex different TCR PubMed Scopus Google diverse can recognise the distinct surface et the antigenic of Google Scholar, et of an of the PubMed Scopus Google However, an and likely is that the Vδ1 TCR a of This is by the diverse of for et and by of a human T cell antigen receptor to Immunol. PubMed Scopus Google Scholar, et of cell by human TCR-dependent recognition of PubMed Scopus Google Scholar, et of T cells by Immunol. PubMed Scopus Google Scholar, et antigen recognition by the Immunol. 2013; PubMed Scopus Google Scholar, et T cells a microbial B cell antigen to a PubMed Scopus Google 1). major is to of of and the for remained on the that clonal the adaptive paradigm we suggests a of on phenotype, and by which the of within adaptive be of γδ T cell in of these to et of T cells by Immunol. PubMed Scopus Google and et antigen recognition by the Immunol. 2013; PubMed Scopus Google Scholar, et of T cells in human a Immunol. PubMed Scopus Google Scholar, et of T cell receptor in complex with recognition of a by human T 2013; PubMed Scopus Google described to of the Vδ1 T cell repertoire and of T cells, they are to in expanded Vδ1 Teffector However, they from Vδ1 Tnaïve and in in different Vδ1 clonal et T cells a microbial B cell antigen to a PubMed Scopus Google Scholar], a antigen from a also to be a γδ TCR in and for an of the human Vδ1 T cell repertoire of T cells, recognition by expanded Vδ1 Teffector this, recognition the of Vδ1 to recognise in human γδ TCR to et and by of a human T cell antigen receptor to Immunol. PubMed Scopus Google Scholar], the for recognition by an expanded Vδ1 Teffector involving a TCR 1). the TCR that a private TCR in with the of Vδ1 and the that recognition of to a this, γδ TCR and recognition of cells. by γδ T cell on a which of of on target cells infection et and by of a human T cell antigen receptor to Immunol. PubMed Scopus Google in is also that of is to et receptor is in as a of and of PubMed Scopus Google Scholar], and also to et of the cell receptor in PubMed Scopus Google the of effector function on in to the presence of TCR be an in the of γδ T cell in the of microbial non-microbial as the to be but private private expanded on γδ TCR expanded in response to a immune this, and between on a to the specific pathogen of γδ be for involving of the of the of target for γδ T cell receptors. studies in by the of these to clonal expansion of Vδ1 T cells, the that major Vδ1 Teffector that immune stimuli, specific Vδ1 with this, have with of T cells, including et cell receptor lymphocyte Immunol. Google Scholar], et T cells in 2013; PubMed Scopus Google Scholar, et T cell receptor repertoire of T lymphocytes human cell and the for B cells in clonal Immunol. PubMed Scopus Google Scholar], and microbial 1Hayday A.C. γδ cells: a right time and a right place for a conserved third way of protection.Annu. Rev. Immunol. 2000; 18: 975-1026Crossref PubMed Scopus (956) Google this, the between a pathogen specific Vδ1 clonal and an response to that that the from Vδ1 Tnaïve to Teffector clonal the and of effector Vδ1 Teffector cells and Vδ1 Tnaïve cells Vδ1 Teffector cells and production of and relative to Vδ1 Tnaïve cells et in the human T cell repertoire TCR-dependent adaptive immune PubMed Scopus Google studies have Teffector responses to target cells infection et of T cells cells and PubMed Scopus Google Scholar, alongside an of Vδ1 T cells an effector relative to et expansion of T cells is a specific of PubMed Scopus Google However, an understanding of with is the diverse that underpin the of Vδ1 Teffector of human and and with remained clonal Such also the relative of the and clonal expansion to be The presence of γδ T cells in suggests that for their 1Hayday A.C. γδ cells: a right time and a right place for a conserved third way of protection.Annu. Rev. Immunol. 2000; 18: 975-1026Crossref PubMed Scopus (956) Google to γδ T cell that have recognition highly distinct from αβ T cell involving as et of in cellular by a major human PubMed Scopus Google Scholar, et and human T Immunol. 2013; PubMed Scopus Google and and of T cells et to T cell PubMed Scopus Google Scholar, et is a highly for T PubMed Scopus Google Scholar, is to immune adaptive γδ T cell to the as the expansion of human Vδ1 T cells, a for cells et and cells: the response to Immunol. PubMed Scopus Google and T cells T cell responses to Rev. Immunol. PubMed Scopus Google in However, also immune at of including the MHC et to the immune PubMed Scopus Google Scholar], and of for conserved for as et and cells: the response to Immunol. PubMed Scopus Google of a recombined immune receptor repertoire MHC-unrestricted recognition of diverse and private γδ TCR to cell surface likely and for to also enable recognition of pathogen on the surface of cells. from that γδ T cells as as the T cell et T cells PubMed Scopus Google Scholar, et of infection by T PubMed Scopus Google are with these studies are to understand the of the γδ and the of the recognition in which they are studies have our understanding of Vδ1 T cells. The clonal expansion and differentiation of Vδ1 T cells a that the γδ TCR is likely to be to their but also to that Vδ1 function is by a MHC-unrestricted adaptive This with T cell which to be the of adaptive and innate-like within the human γδ T cell This adaptive for Vδ1 T cells a of and also an which can be which the the of for Vδ1 γδ in the context of adaptive paradigm is but the repertoire and which the paradigm is by which to and is an for the importance of in γδ T cell and et to T cell PubMed Scopus Google Scholar, et is a highly for T PubMed Scopus Google Scholar, et of by Rev. Immunol. PubMed Scopus Google the of in human γδ T cell in the context of innate-like and adaptive-like is understanding of human γδ T cell of their understanding of γδ TCR is in γδ T cells, in the least to their MHC-unrestricted recognition of target cells and cytotoxic the to Vδ1 Tnaïve from Teffector a to Vδ1 T cell responses diverse microbial and non-microbial at different which an the the of γδ T cell the Vδ1 is Vδ1 clonal in lymphoid in peripheral which cells are adaptive Vδ1 responses they for αβ T cell responses are as in from which clonal is the of and which non-microbial can Vδ1 responses in is expanded Vδ1 they of that to are the private to each and they to each are the Vδ1 of focussed in pathogen are in the Vδ1 of with to specific the repertoire and of Vδ1 T cells in to peripheral Vδ1 T they with adaptive Vδ1 in peripheral are they and they also as in tissue-associated γδ T a for in the antigenic of the Vδ1 T cell innate-like adaptive Vδ1 are Vδ1 T they be as in the Vδ1 is Vδ1 clonal in lymphoid in peripheral which cells are adaptive Vδ1 responses they for αβ T cell responses are as in from which clonal is the of and which non-microbial can Vδ1 responses in is expanded Vδ1 they of that to are the private to each and they to each are the Vδ1 of focussed in pathogen are in the Vδ1 of with to specific the repertoire and of Vδ1 T cells in to peripheral Vδ1 T they with adaptive Vδ1 in peripheral are they and they also as in tissue-associated γδ T a for in the antigenic of the Vδ1 T cell innate-like adaptive Vδ1 are Vδ1 T they be as in and for This by to and