THE T-CELL RECEPTOR REPERTOIRE INFLUENCES V-BETA ELEMENT USAGE IN RESPONSE TO MYOGLOBIN

T cell clones recognizing the sperm whale myoglobin (SpWMb) epitope 110-121 in association with H-2(d) major histocompatibility complex class 11 molecules display a very limited heterogeneity of T cell receptor (TCR) V-beta usage in DBA/2 mice. All clones previously tested used the same V-beta 8.2 gene segment and very restricted junctional regions. To investigate the significance of this observation in vivo, we immunized DBA/2 mice with the intact SpWMb protein or peptide 110-121. Only the V-beta-8+ T cells showed any significant response to the 110-121 epitope. The response to peptide 110-121 was then analyzed in mice which, either as a consequence of antibody depletion or through genetic deletion of TCR V-beta genes, lacked V-beta-8+ peripheral T cells. DBA/2 mice depleted of V-beta-8+ T cells by antibody treatment responded poorly to the 110-121 peptide, and only at high antigen concentrations. In contrast, DBA/2V-beta-a mice (homozygous for a deletion of multiple V-beta gene segments including the V-beta-8 family) made a response at least as great as that made by DBA/2 mice, even though the DBA/2V-beta-a mice had a very restricted TCR V-beta repertoire compared with DBA/2 mice. Mechanisms which might determine differences in the 110-121 specific response of DBA/2, DBA/2V-beta-1 and F23.1-treated DBA/2 mice are discussed.