TY - JOUR
T1 - The role of structurally conserved class I MHC in tumor rejection
T2 - Contribution of the Q8 locus
AU - Chiang, Eugene Y.
AU - Stroynowski, Iwona
PY - 2006/8/15
Y1 - 2006/8/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33746876730&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33746876730&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.177.4.2123
DO - 10.4049/jimmunol.177.4.2123
M3 - Article
C2 - 16887971
AN - SCOPUS:33746876730
SN - 0022-1767
VL - 177
SP - 2123
EP - 2130
JO - Journal of Immunology
JF - Journal of Immunology
IS - 4
ER -