Somatic hypermutation of the T cell receptor V beta gene in microdissected splenic white pulps from HIV-1-positive patients.
Somatic mutation of rearranged immunoglobulin V genes occurs in germinal centers (GC), resulting in affinity maturation of the immune response. Rearranged T cell receptor (TCR) genes were thought to be excluded from this process despite similarities in their gene structure. Somatic mutations were found among TCR V alpha (TCRAV) chains of antigen-specific T cells localized in GC of mice. Here, somatically mutated TCR V beta 3 (TCRBV) chains are identified among microdissected splenic white pulps from HIV-positive individuals. Both the frequency and the nature of the base substitutions were found to be similar to those of mutated immunoglobulin VH genes. This was true for intrinsic mutations in the TCR framework regions as well as for mutations underlying selective pressures in the TCRBV5 gene segment. The concentration of mutations and a preference for replacement mutations in complementarity determining regions of expanded clones were indicative of a positive selection process.
Cheynier
R
R
Unité de Rétrovirologie Moléculaire, Institut Pasteur, Paris, France.
Henrichwark
S
S
Wain-Hobson
S
S
D001483:Base Sequence; D002460:Cell Line; D004210:Dissection; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006679:HIV Seropositivity / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000276:immunology*; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D013154:Spleen / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D013156:Splenectomy; D013602:T-Lymphocytes, Cytotoxic
D017260:Receptor-CD3 Complex, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta