The role of structurally conserved class I MHC in tumor rejection: Contribution of the Q8 locus

Eugene Y. Chiang, Iwona Stroynowski

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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 α1 and α2 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.

Original languageEnglish (US)
Pages (from-to)2123-2130
Number of pages8
JournalJournal of Immunology
Volume177
Issue number4
DOIs
StatePublished - Aug 15 2006

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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