The T-cell receptor V beta 6 gene usage in alloreactive T-cell responses.
To analyze the role of TCR V beta gene elements in allorecognition, we have determined frequencies of the TCR V beta 6 elements expressed by allospecific T cells as compared to randomly activated T cells. Limiting dilution analysis was applied to estimate the usage of TCR V beta elements in CD4+ T cells polyclonally stimulated by immobilized anti-CD3 or specifically activated with HLA-DR disparate allotargets. In a focused alloresponse of HLA-DRB1*0401+ responders to HLA-DRB1*0404+ stimulator cells, V beta 6+ T cells were preferentially recruited. To map the functional domain of allogeneic HLA-DR molecules involved in the recruitment of V beta 6+ T-cell specificities, CD4+ T cells from HLA-DRB1*0401+ donors were activated with allogeneic stimulators sharing either the first and second or the third HVR of the HLA-DRB1 gene. Stimulation with allotargets sharing the sequence of the HVR3 caused a twofold to fourfold enrichment of V beta 6+ CD4+ T cells, while sequence variations in the HVR3 was sufficient to abrogate the preferential usage of V beta 6+ T cells. These data suggest that sequence variations mapped to the alpha-helical loop of the HLA-DR beta chain impose structural constraints that shape the alloreactive TCR V beta repertoire.
Hu
W
W
Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Weyand
C M
CM
Goronzy
J J
JJ
D000483:Alleles; D000595:Amino Acid Sequence; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002460:Cell Line; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008214:Lymphocytes; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553505:HLA-DRB1*04:01 antigen; D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta