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

作者：Gras Stephanie; Burrows Scott R; Turner Stephen J; Sewell Andrew K; McCluskey James; Rossjohn Jamie^*

来源：Immunological Reviews, 2012, 250(1): 61-81.

DOI：10.1111/j.1600-065X.2012.01159.x

• T-cell receptor
• major histocompatibility complex
• protective immunity
• aberrant immunity

T cells that express clonally distributed a beta 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.

• 出版日期2012-11
• 单位河北医科大学