A structural voyage toward an understanding of the MHC-I-restricted immune response: lessons learned and much to be learned

Stephanie Gras, Scott R Burrows, Stephen J Turner, Andrew K Sewell, James McCluskey, Jamie Rossjohn

Research output: Contribution to journalArticleResearchpeer-review

63 Citations (Scopus)

Abstract

T cells that express clonally distributed alphabeta T-cell receptors (TCRs) corecognize antigenic peptides (p) bound to major histocompatibility complex class I (MHC-I) and class II molecules (MHC-II). Extensive human leukocyte antigen (HLA) polymorphism enables HLA molecules from different haplotypes to capture an array of self- and microbe-derived peptide antigens that is fundamental to adaptive immunity. T cells developing in the thymus are selected for weak binding to self-peptide-HLA complexes generating a vast repertoire of clonally distinct T cells in the periphery. Indeed, diversity within germline loci and the finally assembled TCR genes, coupled with inherent TCR cross-reactivity, enables CD8(+) T cells to survey the multitude of pHLA-I landscapes. Precisely how does the TCR ligate to pHLA-I, and how does knowledge of the detailed structural interactions inform immunobiology? A recent number of our structural studies concerning the TCR-pMHC-I axis, alongside others in the field, have provided insight into HLA-I polymorphism, pMHC-I flexibility, TCR bias, TCR polymorphism, maintenance of self-tolerance, T-cell cross-reactivity, and alloreactivity. Collectively, the data also provide an opportunity to address the structural correlates of MHC-I restriction. Here, we provide our perspective concerning these advances in the field. Although much key information has been gleaned, the structural data show that some of the key concepts surrounding the TCR-pMHC-I interaction remain controversial and unresolved.
Original languageEnglish
Pages (from-to)61 - 81
Number of pages21
JournalImmunological Reviews
Volume250
Issue number1
DOIs
Publication statusPublished - 2012

Cite this

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title = "A structural voyage toward an understanding of the MHC-I-restricted immune response: lessons learned and much to be learned",
abstract = "T cells that express clonally distributed alphabeta T-cell receptors (TCRs) corecognize antigenic peptides (p) bound to major histocompatibility complex class I (MHC-I) and class II molecules (MHC-II). Extensive human leukocyte antigen (HLA) polymorphism enables HLA molecules from different haplotypes to capture an array of self- and microbe-derived peptide antigens that is fundamental to adaptive immunity. T cells developing in the thymus are selected for weak binding to self-peptide-HLA complexes generating a vast repertoire of clonally distinct T cells in the periphery. Indeed, diversity within germline loci and the finally assembled TCR genes, coupled with inherent TCR cross-reactivity, enables CD8(+) T cells to survey the multitude of pHLA-I landscapes. Precisely how does the TCR ligate to pHLA-I, and how does knowledge of the detailed structural interactions inform immunobiology? A recent number of our structural studies concerning the TCR-pMHC-I axis, alongside others in the field, have provided insight into HLA-I polymorphism, pMHC-I flexibility, TCR bias, TCR polymorphism, maintenance of self-tolerance, T-cell cross-reactivity, and alloreactivity. Collectively, the data also provide an opportunity to address the structural correlates of MHC-I restriction. Here, we provide our perspective concerning these advances in the field. Although much key information has been gleaned, the structural data show that some of the key concepts surrounding the TCR-pMHC-I interaction remain controversial and unresolved.",
author = "Stephanie Gras and Burrows, {Scott R} and Turner, {Stephen J} and Sewell, {Andrew K} and James McCluskey and Jamie Rossjohn",
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A structural voyage toward an understanding of the MHC-I-restricted immune response: lessons learned and much to be learned. / Gras, Stephanie; Burrows, Scott R; Turner, Stephen J; Sewell, Andrew K; McCluskey, James; Rossjohn, Jamie.

In: Immunological Reviews, Vol. 250, No. 1, 2012, p. 61 - 81.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Burrows, Scott R

AU - Turner, Stephen J

AU - Sewell, Andrew K

AU - McCluskey, James

AU - Rossjohn, Jamie

PY - 2012

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