Structure and repertoire usage of rat TCR alpha-chain genes in T cells infiltrating heart allografts.
We have studied the structure and diversity of TCR alpha-chain genes used by graft-infiltrating lymphocytes (GIL) in the ACI-to-LEW rat cardiac allograft model. We previously reported the structure of 16 different V alpha and 17 different J alpha genes isolated in two different cDNA libraries established from LEW thymocytes and GIL. In this report, we obtained new sequence information for 17 additional V alpha and J alpha genes from the GIL cDNA library. This study completes our characterization of 33 different V alpha and 23 different J alpha genes in rats. The V alpha genes are classified into 14 different families. Nucleotide sequence comparison with mouse alpha genes revealed the existence of mouse homologues for all the J alpha and 32 of the 33 V alpha genes. One of the rat V alpha genes seemed to have no known mouse counterpart and is classified here as a V alpha 24 gene family. The definition of rat TCR alpha-chain genes derived from these studies should facilitate a better understanding of the T cell role in pathologic conditions including autoimmune diseases and graft rejection. As for the TCR alpha-chain repertoire usage in allograft rejection, we completed the characterization of 36 productively rearranged TCR alpha-chain cDNA clones from the GIL cDNA library and found 31 different V alpha and 23 different J alpha genes among these clones. Unlike the TCR beta-chain that uses a limited repertoire, the alpha-chain repertoire usage seems to be relatively more diverse in this allograft model. These results suggest that the interaction of beta-chain with allogeneic MHC-encoded determinants may dictate the T cell reaction to the heart allograft in this model.
Department of Surgery, Cedars-Sinai Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048.
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Shirwan
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Barwari
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Fuss
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Makowka
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Cramer
D000005:Abdomen; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018076:DNA, Complementary / Q000235:genetics; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D008969:Molecular Sequence Data; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D016415:Sequence Alignment; D017385:Sequence Homology; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology*; D016042:Transplantation, Heterotopic; D014184:Transplantation, Homologous / Q000276:immunology / Q000473:pathology
D018076:DNA, Complementary; D016693:Receptors, Antigen, T-Cell, alpha-beta