The role of structurally conserved class I MHC in tumor rejection: contribution of the Q8 locus.
The mouse multimember family of Qa-2 oligomorphic class I MHC genes is continuously undergoing duplications and deletions that alter the number of the two "prototype" Qa-2 sequences, Q8 and Q9. The frequent recombination events within the Q region lead to strain-specific modulation of the cumulative Qa-2 expression levels. Q9 protects C57BL/6 hosts from multiple disparate tumors and functions as a major CTL restriction element for shared tumor-associated Ags. We have now analyzed functional and structural properties of Q8, a class I MHC that differs significantly from Q9 in the peptide-binding, CTL-interacting alpha(1) and alpha(2) regions. Unexpectedly, we find that the extracellular domains of Q8 and Q9 act similarly during primary and secondary rejection of tumors, are recognized by cross-reactive antitumor CTL, have overlapping peptide-binding motifs, and are both assembled via the transporter associated with the Ag processing pathway. These findings suggest that shared Ag-presenting functions of the "odd" and "even" Qa-2 loci may contribute to the selective pressures shaping the haplotype-dependent quantitative variation of Qa-2 protein expression.
Chiang
Eugene Y
EY
Center for Immunology, Department of Microbiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Stroynowski
Iwona
I
D000818:Animals; D001665:Binding Sites / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D017124:Conserved Sequence; D045142:Cross-Priming / Q000235:genetics / Q000276:immunology; D045604:Extracellular Fluid / Q000276:immunology; D005819:Genetic Markers / Q000276:immunology; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology*; D006183:H-2 Antigens / Q000737:chemistry* / Q000235:genetics* / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D014162:Transfection
D005819:Genetic Markers; D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I; D010455:Peptides; C032907:Q surface antigens