Localization of structural variations distinguishing I-Ak-related molecules to the alpha 1 and beta 1 domains.
The structural variations that distinguish the A molecules encoded by wild-derived H-2 complexes which express Ak-related molecules have been localized into the alpha 1 and beta 1 domains by radiochemical sequence analyses of tryptic peptides. The A alpha subunits of B10.STC90 (Akv1) and W12A (Akv2) differ from those of B10.BR (Ak) in two adjacent tryptic peptides spanning positions 43 to 71 in the alpha 1 domain. The A beta subunit of W12A differs from that of B10.BR in two peptides spanning positions 26 to 29 and 95 to 106. Isoleucine and leucine residues present at positions 28 and 95, respectively, in the B10.BR A beta subunit are not found in the corresponding positions in W12A A beta subunits. Both of these A beta sequence variations are in the beta 1 domain. B10.STC90 A beta subunits are identical to those of W12A except for a structural variation in the beta 1 domain affecting the HPLC retention time of a peptide spanning positions 49 to 63. These results suggest that these A molecules are encoded by closely related class II gene alleles which have diversified by the accumulation of discrete mutations within the exons encoding the alpha 1 and beta 1 domains of the A molecule. Our previous functional analyses of these minor variant A molecules have demonstrated that they are readily distinguished with A molecule-specific alloreactive T lymphocytes. Together, these findings suggest that minor structural variations in the alpha 1 and beta 1 domains of the A molecule can dramatically modify the allodeterminants recognized by alloreactive T lymphocytes.
D000595:Amino Acid Sequence; D000818:Animals; D005796:Genes; D005802:Genes, MHC Class II; D014644:Genetic Variation; D006183:H-2 Antigens / Q000235:genetics; D064532:Histocompatibility Antigen H-2D; D000949:Histocompatibility Antigens Class II / Q000145:classification / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D010446:Peptide Fragments; D011110:Polymorphism, Genetic; D014357:Trypsin
D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; D014357:Trypsin