CONSERVED TCR BETA-CHAIN USAGE FOR A SINGLE MHC CLASS II-RESTRICTED HEAT-SHOCK-PROTEIN PEPTIDE

Previously we have shown that the T-cell response against the HLA-DR3 (17)-restricted heat shock protein (M-r 65 000)-derived peptide amino acids (aa) 3-13 (hsp65 aa 3-13) is recognized by the exclusive usage o f the TRBV5 gene as well as a conserved CDR3 region in a tuberculoid l eprosy patient. In the present study we analyzed the TcR of T-cell clo nes specific for hsp65 aa 3-13 derived from three healthy individuals with a response level similar to that of the leprosy patient. We show that unlike the tuberculoid leprosy patient, healthy high responders h ave a diverse T-cell response to hsp65 aa 3-13. However, a striking ob servation was made: even though high responders have a diverse specifi c TcR repertoire, TRBV5-expressing clones from two healthy individuals could be isolated that were nearly identical to a dominant clone in t he tuberculoid leprosy patient. In conclusion, the data show that rest riction of TcR specific for an antigen correlates with the presence of that antigen in disease. However, the preferred TcR can also be detec ted in healthy high responders. A natural infection in vivo, as with t he tuberculoid leprosy patient, may be responsible for the observed tr imming and preferential outgrowth of a certain TcR.