Immunodominance correlates with T-cell receptor (alpha beta) gene usage in the class II-restricted response to influenza haemagglutinin.
Class II-restricted T-cell clones elicited by natural infection with influenza A virus (H3N2 subtype) exhibit extensive diversity in their recognition specificity for the envelope glycoprotein, haemagglutinin, and focus on hypervariable regions of the HA1 subunit that feature in antigenic drift. However, T-cell clones established from the same individual focus on a single antigenic site with differing fine specificity for mutant viruses. We wished to determine whether such diversity of the haplotype and contrasting immunodominance of the individual's repertoire was mirrored in T-cell receptor (TcR) gene usage. A structural analysis was undertaken of the alpha and beta chains of TcR from a panel of CD4+ T-cell memory clones established in vitro after natural infection with X31 virus and specific for eight distinct antigenic sites of the HA1 subunit: p48-67 (Ak), p58-73 (Ad), p120-139 (Ak), p177-199 (Ad), p186-200 (Ad), p226-245 (Ek), p246-265 (Ek) and p269-288 (Ak). Direct sequencing of the alpha and beta chains, using the polymerase chain reaction, revealed that T-cell clones derived from the same donor used identical V beta D beta J beta and V alpha J alpha elements. Moreover there was extensive diversity in usage of V beta (V beta 1 or V beta 4 or V beta 8) genes between individual mice, in association with diverse J beta and V alpha J alpha elements for the recognition of a common antigenic peptide. We conclude that the CD4+ T-cell memory repertoire of the individual, following primary exposure to infectious virus, is oligoclonal and recruited from a limited number of precursor cells.
National Institute for Medical Research, London, U.K.
C A
CA
Smith
C M
CM
Graham
D B
DB
Thomas
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D002999:Clone Cells / Q000276:immunology; D015329:Gene Rearrangement, T-Lymphocyte / Q000276:immunology; D014644:Genetic Variation; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics*
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D000949:Histocompatibility Antigens Class II; D016693:Receptors, Antigen, T-Cell, alpha-beta