Degeneracy of T cell receptor recognition of an influenza virus hemagglutinin epitope restricted by HLA-DQ and -DR class II molecules.
DT9301-0229737 the TcR are believed to provide the peptide fragments bound to major histocompatibility (MHC) molecules. TcR have an immunoglobulin (Ig)-like structure and, in an analogous manner to antigen recognition by Ig, the third complementarity determining regions (CDR3) of the TcR are believed to provide the primary contact with the peptide lying in the MHC groove. CDR1 and CDR2 are thought to contact the presenting MHC molecule. We have analyzed seven human CD4+ T cell clones that recognize a conserved peptide epitope (residues 255-270) within the influenza virus hemagglutinin (H3) HA1 subunit. Two T cell clones recognized the peptide in the context of HLA-DRB1*1001 and HLA-DQB1*0602/DQA1*0102, respectively, and shared V alpha, V beta and J beta gene segments. Only the junctional regions encoding the CDR3 regions of the two TcR chains were different. This suggests that the CDR3 regions of these TcR interact with the MHC class II molecule. Six of the T cell clones were restricted by the HLA-DRB1*1001. Two of these T cell clones expressed V beta 9.1 and three expressed V beta 13 gene segments; the remaining clone expressed V beta 7.2, a close homologue of V beta 9.1. A diverse selection of V alpha and J gene segments contributed to the junctional heterogeneity of the TcR, indicating a diversity of sequence combinations recognizing the epitope. Nevertheless, five out of six T cell clones bore a motif in the V alpha CDR3 loop consisting of adjacent acidic and polar amino acid residues, eight residues from the carboxyl end of each CDR3.
Jones
C M
CM
Department of Immunology, St. Mary's Hospital Medical School, London, GB.
Lake
R A
RA
Lamb
J R
JR
Faith
A
A
D000595:Amino Acid Sequence; D002461:Cell Line, Transformed; D018076:DNA, Complementary / Q000302:isolation & purification; D000939:Epitopes / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology*; D006389:Hemagglutinins, Viral / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009975:Orthomyxoviridae / Q000276:immunology; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology
D018076:DNA, Complementary; D000939:Epitopes; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D006389:Hemagglutinins, Viral; D016693:Receptors, Antigen, T-Cell, alpha-beta