Analysis of T cell receptors specific for recognition of class IB antigens

T cells that recognize a peptide presented by a self-class IA molecule generally use a restricted repertoire of Vβ and Vα 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 Vβ chains specific for Qa-1 and similar sequences in both Vβ and Vα chains specific for Qa-2. We observed that 14 Qa-1-specific clones use a limited number of Vβ segments and 8 of 14 express Vβ8.2 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 Jβ 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 αβ T cell repertoire. The α- and β-chains from nine alloreactive anti-Qa-2 clones were analyzed. Vβ use was limited to use of Vβ7 or a member of the Vβ8 family. Rearrangements were solely to the second Jβ cluster. The use of Vα and Jα segments were diverse. Although conserved residues or motifs were observed in the CDR3 regions of both the β- and α-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.