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Murray JS. An old Twist in HLA-A: CDR3α Hook up at an R65-joint. Front Immunol. 2015;6:268doi: 10.3389/fimmu.2015.00268.
Murray, J. S. (2015). An old Twist in HLA-A: CDR3α Hook up at an R65-joint. Frontiers in immunology, 6268. https://doi.org/10.3389/fimmu.2015.00268
Murray, Joseph S. "An old Twist in HLA-A: CDR3α Hook up at an R65-joint." Frontiers in immunology vol. 6 (2015): 268. doi: https://doi.org/10.3389/fimmu.2015.00268
Murray JS. An old Twist in HLA-A: CDR3α Hook up at an R65-joint. Front Immunol. 2015 May 27;6:268. doi: 10.3389/fimmu.2015.00268. eCollection 2015. PMID: 26074926; PMCID: PMC4445401.
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Front Immunol. 2015 May 27;6:268. doi: 10.3389/fimmu.2015.00268. eCollection 2015.

An old Twist in HLA-A: CDR3α Hook up at an R65-joint.

Frontiers in immunology

Joseph S Murray

Affiliations

  1. Xenolaüs Genetics LLC , Los Angeles, CA , USA.

PMID: 26074926 PMCID: PMC4445401 DOI: 10.3389/fimmu.2015.00268

Abstract

T-cell ontogeny optimizes the α/β T-cell receptor (TCR) repertoire for recognition of major histocompatibility complex (MHC) class-I/II genetic polymorphism, and co-evolution of TCR germline V-gene segments and the MHC must entail somatic diversity generated in the third complimentary determining regions (CDR3α/β); however, it is still not clear how. Herein, a conspicuous structural link between the V-Jα used by several different TCR [all in complex with the same MHC molecule (HLA-A2)], and a conserved MHC motif (a.a., R65-X-X-K-A-X-S-Q72) is described. We model this R65-joint in detail, and show that the same TCR's CDR3α loop maintains its CDR2α loop at a distance of ~4 Å from polymorphic amino acid (a.a.) positions of the α-2 helix in all but one of the analyzed crystal structures. Indeed, the pitch of docked TCRs varies as their twist/tilt/sway maintains the R65-joint and peptide contacts. Thus, the R65-joint appears to have poised the HLA-A lineage toward alloreactivity.

Keywords: HLA; MHC; TCR; alloreactivity; evolution; immunogenetics; placentation; primate

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