A third class I major histocompatibility complex antigen encoded by a gene in the D region of the H-2 d haplotype recognized by cytotoxic T lymphocytes

Abstract

The D region of the H-2d haplotype contains five class I genes: H-2Dd, D2d, D3d, D4d and H-2Ld. Although previous studies have suggested the presence of D-end encoded class I molecules in addition to H-2Dd and H-2Ld, segregation of genes encoding such molecules has not been demonstrated. In this report we have used cytotoxic T lymphocytes (CTL) to examine the D region of the H-2d haplotype for the presence of additional class I molecules. CTL generated in (C3H x B6.K1)F1 (KkDk, KbDb) mice against the hybrid class I gene product Q10d/Ld expressed on L cells cross-react with H-2Ld but not H-2Dd molecules, as determined by lysis of transfected cells expressing H-2Ld but not H-2Dd. Although H-2Ld-specific monoclonal antibodies (mAb) completely inhibit H-2Ld-specific CTL from killing B10.A(3R) (KbDdLd) target cells, only partial inhibition of anti-Q10 CTL-mediated lysis was observed, suggesting the presence of an additional D-end molecule as a target for these latter CTL. To identify the region containing the gene encoding the Q10 cross-reactive molecule, we show that anti-Q10 CTL lyse target cells from a D-region recombinant strain B10.RQDB, which has H-2Dd, D2d, D3d, D4d, and H-2Db but not the H-2Ld H-2d, and H-2Ld (including D2d, D3d, and D4d), lacks this anti-Q10 CTL target molecule. Together, these data demonstrate that a class I gene mapping between H-2Dd and H-2Ld encodes an antigen recognized by anti-Q10 CTL. A likely candidate for this gene is D2d, D3d, or D4d.

MHC antigen induction by interferon gamma on cultured mouse pancreatic beta cells and macrophages. Genetic analysis of strain differences and discovery of an "occult" class I-like antigen in NOD/Lt mice.

“…Since the Hh-1 locus is apparently in tight linkage with H-2D it is tempting to speculate that Hh-1 may be one of the class I genes that have been mapped to the H-2D locus in addition to the standard H-2D gene . Like the occult antigen in this report, the products of these genes (D2, D3, and D4) have recently been demonstrated to be capable o£ being recognized by CTL (29). Other genes with low polymorphism, but with broad expression in epithelial tissues have been reported (30) such that the exact identity of the structural gene encoding the occult antigen remains to be determined.…”

An immunodominant epitope present in multiple class I MHC molecules and recognized by cytotoxic T lymphocytes.

“…However, by shuffling the first three exons of Q10d with the latter five exons of H-2L", a hybrid molecule can be expressed on the cell membrane of transfected L cells containing the al and a2 domains of Q10 together with the carboxy-end of the molecule derived from H-2Ld (31) . We recently showed CTL activity can be generated against this molecule and it is specific for determinants controlled by the al and a2 and not the H-2Ld-encoded 0 domain (29,30). Since Q10 shares the H-2Kbm 1 mutant amino acids at positions 152, 155, and 156 (see Table III), we tested whether anti-Q10 CTL would crossreact on H-2Kbm', Anti-Q10 CTL were generated by stimulating spleen cells from (C3H x B6.K1)F1 (K''D'F/KbDb) mice with L cells (H-2k) expressing the Q10d/L d hybrid molecule .…”

Glycosylphosphatidylinositol‐anchored H‐2Db molecules are defective in antigen processing and presentation to cytotoxic T lymphocytes

“…The extracellular domains of Qa-2 are greater than 90% identical in sequence to Db [29], bind peptides that have a common motif [31,32], and can be recognized by allospecific CTL [33]. Nevertheless, Qa-2 has never been shown experimentally to act as a restriction element.…”