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 germin al centers (GC), resulting in affinity maturation of the immune respon se. Rearranged T cell receptor (TCR) genes were thought to be excluded from this process despite similarities in their gene structure. Somat ic mutations were found among TCR V alpha (TCRAV) chains of antigen-sp ecific T cells localized in GC of mice. Here, somatically mutated TCR V beta (TCRBV) chains are identified among microdissected splenic whit e pulps from HIV-positive individuals. Both the frequency and the natu re of the base substitutions were found to be similar to those of muta ted immunoglobulin VH genes. This was true for intrinsic mutations in the TCR framework regions as well as for mutations underlying selectiv e pressures in the TCRBV5 gene segment. The concentration of mutations and a preference for replacement mutations in complementarity determi ning regions of expanded clones were indicative of a positive selectio n process.