IMMUNODOMINANCE OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I-RESTRICTED INFLUENZA-VIRUS EPITOPES CAN BE INFLUENCED BY THE T-CELL RECEPTOR REPERTOIRE

We have used T-cell receptor beta-chain transgenic mice to determine t he effects of a limited T-cell receptor repertoire on major histocompa tibility complex class I-restricted epitope selection during the cours e of an influenza virus infection. Analysis of T-cell hybridomas gener ated from wild-type and transgenic mice demonstrated that the viral ep itope recognized depended on the available T-cell receptor repertoire. Wild-type T-cell hybridomas recognized epitopes derived from the nucl eoprotein and basic polymerase molecules, whereas hybridomas generated from transgenic mice recognized epitopes derived from the nonstructur al protein and the matrix protein, There was no overlap in specificity between the two panels of hybridomas. This reciprocal pattern of spec ificity was also apparent in cytotoxicity assays with bronchoalveolar lavage cells isolated from the lungs of influenza virus-infected mice. T-cell receptor usage in the transgenic hybridomas was very restricte d, with only one V alpha element used for each of the two viral epitop es recognized. In the case of the hybridomas reactive to the nonstruct ural protein, sequence analysis showed that they all expressed V alpha 4J alpha 32 chains associated with the same junctional amino acids (L eu-Leu) that were encoded by five different nucleotide sequences, indi cating a strong selection for T-cell receptor usage, Taken together, t hese data demonstrate that the available T-cell receptor repertoire ca n have a profound effect on the immunodominance of class I-restricted epitopes during a viral infection.