Complexity of the T cell receptor CP isotypes in the Mexican axolotl: structure and diversity of the VDJC beta 3 and VDJC beta 4 chains

We have reported previously the presence of two T cell receptor beta -chain constant region (C beta) isotypes in the Mexican axolotl. Specific D beta and J beta segments were present at the V beta -C beta1 and V beta -C beta2 junctions and nine V beta families which associate with both isotypes were characterized. This report describes two new C beta isotypes, C beta3 and C beta4. About 70 % of the amino acids in C beta3 are identical to C beta1 and C beta2. A D beta3 and a single J beta3 were found at the V beta -C bet a3 junctions. The D beta3 consensus core sequence (TACGTGGCTACGTGGG) differ s to all the presently known D beta and the CDR3 beta loops of the V beta - C beta3 junctions (mean: 11.1 amino acids) contain a majority of aromatic, small hydrophobic and basic residues. The CDR3 beta loops of the other isot ypes are shorter (mean: 8.5 amino acids), contain a majority of acidic resi dues and very few aromatic residues. The axolotl C beta4 sequence has about 46 % similarity to C beta1, C beta2 and C beta3. D beta4 is identical to D beta2 and six new J beta segments are used at the V beta -C beta4 junction s. Four new families of V beta segments (V beta 10-V beta 13) are preferent ially associated to C beta4. A strong selective pressure must operate in mo st vertebrates to preserve the structural stability of the extracellular pa rt of the C beta chain. The four axolotl C beta seem to have evolved more f reely, perhaps to favor the early emergence of a large diversity of T cell receptors in an amphibian species which is not fully immunocompetent before the 5th month of development.