PUBLIC AND PRIVATE V-BETA T-CELL RECEPTOR REPERTOIRES AGAINST HEN EGG-WHITE LYSOZYME (HEL) IN NONTRANSGENIC VERSUS HEL TRANSGENIC MICE

We have previously produced a transgenic mouse line for hen egg lysozy me (HEL), an experimental model for analyzing tolerance to self-antige ns at the peptide level. We have now characterized transgenic mice wit h HEL blood levels below 2 ng/ml, where significant T cell proliferati ve responses to HEL and its immunodominant peptide were observed. This HEL-low transgenic model was chosen because it mimics physiological c onditions in which autoreactive T lymphocytes, recognizing self-compon ents expressed at very low levels, persist without inducing a break in tolerance. Furthermore, in H-2(d) mice, HEL-specific T lymphocytes ar e triggered by a single immunodominant region, allowing us to compare the HEL-specific T cell V beta repertoires of transgenic and nontransg enic animals against a single peptide presented as self or foreign, re spectively. We found that a V beta 8.2-D beta 1-J beta 1.5 rearrangeme nt is found in response to HEL in all nontransgenic mice, whereas this V beta-restricted response is absent in HEL-low transgenic animals. A t the nucleotide level, this rearrangement results from the trimming o f the genomic segments during VDJ or DJ joining, without N additions, suggesting that the dominant rearrangement is selected early during fe tal or neonatal life, before the expression of terminal deoxynucleotid yl transferase. In HEL-low transgenic mice, no dominant rearrangements are found as alternatives to the one observed in normal mice. Instead , each transgenic animal uses a different set of V beta-J beta combina tions in its response to the immunodominant HEL peptide. In nontransge nic mice, besides the dominant V beta 8.2-D beta 1-J beta 1.5 combinat ion, minor V beta repertoires were found which differed in each animal and were distinct from the rearrangements used by individual transgen ic mice. These findings suggest that the T cell response to an immunod ominant peptide involves a ''public'' V beta repertoire found in all a nimals and a ''private'' one which is specific to each individual.