Analysis of the T-Cell Receptors Utilized for Allogeneic HLA-DR Recognition: Comparison of Different Responder-Cell Donors Possessing an Identical HLA-DR Allele

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Abstract
We examined whether individuals with an identical HLA-DR type utilized the same T-cell receptors (TCRs) to recognize a given allogeneic HLA-DR molecule. CD4+ T cells from three responder-cell donors possessing the DRB*0901 allele were stimulated with HLA-DRB1*0406 molecules, subjected to the primary mixed lymphocyte reaction (MLR) and the TCRs of the activated CD4+ T cells were analysed using single strand conformation polymorphism (SSCP) and random cDNA clone sequencing. The responder cells of each donor yielded many dominant SSCP bands in several TCRAV and TCRBV segments, but none of these dominant SSCP bands derived from two or three responders. Random cDNA sequence analysis demonstrated that the alloreactive TCRs were diverse, but each of the three responder-cell donors showed some dominant cDNA clones. However, no amino acid sequence identities or similarities among the dominant cDNAs of these donors were detected. These results indicate that certain T-cell clones from each individual's TCR repertoire pool expand preferentially as a result of allogeneic HLA-DR recognition but these clones are not necessarily common to different individuals, even when their responder cells possess identical DR alleles and are stimulated with the same alloantigen.