Flexibility of the T cell receptor repertoire

Alternative T cell receptor (TcR) gene usage between mice of different Mls alleles has been demonstrated in a number of T cell responses. A clear illustration of a flexible TcR V beta usage in the same strain of mice remains to be established. Using a model system in which I-Ek-restricted T cells recognizing lambda repressor cI protein (cI) 12-26 and pigeon cytochrome c (pcc) 81-104 predominantly use V beta 3 in B10.A and B10.BR mice, and V beta 1 in Mls-2a-bearing A/J and C3H mice, we have first demonstrated that the hierarchy of TcR V beta usage can not be inferred from one strain of mice to the other. The presumed flexibility of V beta 3 to V beta 1 did not exist in B10.BR mice in the given responses. Instead, a switch of dominant TcR from V beta 1/V beta 3 to V beta 8 was identified in C3H and B10.BR mice. In contrast, there was an absolute rigidity in TcR repertoire usage in some mouse strains such as A/J. The lack of flexibility was not due to slow generating kinetics of replacing T cells; since A/J mice treated with staphylococcal enterotoxin A from birth on still responded poorly to cI 12-26 and pcc 81-104. Therefore, whether TcR V beta usage in a T cell response would be flexible or rigid is highly dependent on each strain of mice. However, even the plasticity seen in B10.BR mice is very limited and further tolerance of the V beta 8+ population results in non-responsiveness toward the given antigens.