Differences in antigen processing with haplotype-mismatched MHC class II heterodimers: Aalpha(d)Abeta(b) heterodimers participate in early endosomal processing.
MHC class II heterozygotes form haplotype-mismatched heterodimers (combining alpha and beta chains of different alleles). Transfected L-cells expressing Aalpha(d)Abeta(d) or Aalpha(d)Abeta(b) presented exogenous OVA(323-339) peptide to T cells with similar high efficiency, while Aalpha(b)Abeta(b) was less efficient and Aalpha(b)Abeta(d) was ineffective. In contrast, Aalpha(d)Abeta(b) greatly exceeded Aalpha(d)Abeta(d) in processing of intact OVA for presentation of OVA(323-339); Aalpha(b)Abeta(b) was even less efficient and Aalpha(b)Abeta(d) was ineffective. Of macrophages from C57BL/6 (H-2(b)), DBA/2 (H-2(d)) and B6D2F1 (H-2(bxd))mice, B6D2F1 macrophages had highest I-A expression and efficiency for OVA processing or presentation of exogenous OVA(323-339) peptide. Blocking antibodies specific for I-A chains showed that OVA processing by B6D2F1 macrophages primarily involved haplotype-mismatched Aalpha(d)Abeta(b) heterodimers, whereas Aalpha(d)Abeta(d) and Aalpha(b)Abeta(b) contributed more to presentation of exogenous OVA(323-339) peptide. OVA(323-339):I-A complexes were formed from OVA within 10 min with B6D2F1 macrophages but not until 20 min with C57BL/6 or DBA/2 macrophages, and OVA processing was more resistant to inhibition of late endocytic function by hypothermia (18 degrees C) in B6D2F1 than C57BL/6 or DBA/2 macrophages. These results indicate that Aalpha(d)Abeta(b) haplotype-mismatched heterodimers may contribute to antigen processing in early endocytic compartments.
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D020126:Brefeldin A / Q000494:pharmacology; D019281:Dimerization; D011992:Endosomes / Q000378:metabolism*; D005802:Genes, MHC Class II; D006239:Haplotypes; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006650:Histocompatibility Testing; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000378:metabolism
D000949:Histocompatibility Antigens Class II; D020126:Brefeldin A; D010047:Ovalbumin