Nonrandom T cell receptor usage in the allorecognition of HLA-DR1 microvariation.
Microvariation within the DR1 Ag family has created two DR molecules which differ only at beta-chain residues 85 (Val/Ala) and 86 (Gly/Val). TCR utilized by human alloproliferative T lymphocyte clones which can distinguish between these microvariants have been characterized by cDNA sequencing. The alpha- and beta-chain cDNA utilize a diverse set of variable (V) gene segments although the same V segment may be used by different individuals suggesting that V segment usage by the alloreactive T lymphocyte clones is nonrandom. There appears to be no difference in the repertoire of V segments utilized by T lymphocytes that preferentially recognize specific DR1 allelic products (DR(alpha,beta 1*0101) or DR(alpha,beta 1*0102)) and T lymphocytes that recognize both DR1 molecules. In contrast, the junctional regions of both alpha- and beta-chains are diverse in length and sequence although some common elements can be observed among TCR which share V gene segments. Two TCR which share V alpha and V beta gene segments differ in fine specificity for specific DR1 allelic products implicating the junctional regions of alpha- and beta-chains in the recognition of differentially bound peptides and/or in recognition of DR beta-chain residues 85 and 86. The stimulation of many diverse TCR by the limited allelic variation between DR(alpha,beta 1*0101) and DR(alpha,beta 1*0102) molecules suggests that the effect of DR microvariation on human immune responsiveness may be substantial.
Department of Microbiology, Georgetown University School of Medicine, Washington, DC 20007.
C K
CK
Hurley
N
N
Steiner
A
A
Wagner
M J
MJ
Geiger
D D
DD
Eckels
S
S
Rosen-Bronson
D000595:Amino Acid Sequence; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D015798:HLA-DR1 Antigen / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D016415:Sequence Alignment; D013601:T-Lymphocytes / Q000276:immunology*
D015798:HLA-DR1 Antigen; D009838:Oligodeoxyribonucleotides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D004247:DNA