Analysis of T cell receptors specific for recognition of class Ib antigens.

Abstract

T cells that recognize a peptide presented by a self-class IA molecule generally use a restricted repertoire of V beta and V alpha receptors. In contrast, alloreactive T cells, which recognize alloantigens that present a wide array of peptides, use a diverse repertoire, particularly in the CDR3 loop. Because the T cell repertoire directed against class IB alloantigens is not known, we examined V-D-J sequences in V beta chains specific for Qa-1 and similar sequences in both V beta and V alpha chains specific for Qa-2. We observed that 14 Qa-1-specific clones use a limited number of V beta segments and 8 of 14 express V beta 8.2 and have a conservation of charged residues in the CDR3 loop, particularly between residues 99 and 101. Thirteen of the 14 clones rearrange to the second J beta cluster and use within this cluster is restricted. Alloreactive anti-Qa-1 T cells can be assigned into three different specificity groups based on a Qa-1 modifying gene, Qdm, as well as Qa-1 epitope expression on Tap-2-deficient RMA-S cells. Receptors from members of each specificity group are more similar in their CDR3 loop to each other than members of the other groups. These data lend support to the Qa-1 class IB Ag presenting a limited number of peptides to T cells or in some manner limiting the development of a diverse alpha  beta T cell repertoire. The alpha- and beta-chains from nine alloreactive anti-Qa-2 clones were analyzed. V beta use was limited to use of V beta 7 or a member of the V beta 8 family. Rearrangements were solely to the second J beta cluster. The use of V alpha and J alpha segments were diverse. Although conserved residues or motifs were observed in the CDR3 regions of both the beta- and alpha-chains, the extent of conservation was less than that for anti-Qa-1 receptors. Anti-Qa-2 T cells can be divided into two specificities, Q6 and Q7. No common features were apparent between these groups.