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Differences in antigen processing with haplotype-mismatched MHC class II heterodimers: Aalpha(d)Abeta(b) heterodimers
David Askew1, Clifford V Harding
1Department of Pathology, Case Western Reserve University BRB 925, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
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.
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.