Proteolysis of the heavy chain of major histocompatibility complex class I antigens by complement component C1s.
The major histocompatibility complex (MHC) class I antigens contain a light chain, beta 2-microglobulin, non-covalently associated to the transmembrane heavy alpha-chain carrying the allotypic determinants. Since the C1q complement component is known to associate with beta 2-microglobulin, and we recently found that activated C1s complement was capable of cleaving beta 2-microglobulin, we decided to investigate the proteolytic activity of C1 complement towards the heavy chain of class I antigens. Our results demonstrate that human C1s complement cleaves the heavy chain of human class I antigens into at least two fragments, with apparent molecular weights of 22,000 and 24,000 g/mol on sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), under both reducing and non-reducing conditions. The cleavage of the heavy chain is inhibited by the presence of C1 esterase inhibitor. The molecular weights of the fragments are in agreement with the cleavage located in the area between the disulphide loops of the alpha 2-and alpha 3-domains of the heavy chain. In addition human C1s complement is able to cleave H-2 antigens from mouse in a similar fashion but not rat MHC class I antigen or mouse MHC class II antigen (I-Ad). Mouse MHC class I antigen-specific determinants could also be detected in supernatant from mouse spleen cells incubated with C1r and C1s. These results indicate the presence in the body fluids of a non-membrane-bound soluble form of the alpha 1-and alpha 2-domains which represent the binding site for antigenic peptides.
Eriksson
H
H
Department of Biotechnology, University of Lund, Sweden.
Nissen
M H
MH
D000818:Animals; D001665:Binding Sites; D002846:Chromatography, Affinity; D003173:Complement C1s / Q000494:pharmacology*; D000939:Epitopes / Q000032:analysis*; D006183:H-2 Antigens / Q000302:isolation & purification / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D008285:Major Histocompatibility Complex / Q000187:drug effects*; D051379:Mice; D008970:Molecular Weight; D051381:Rats
D000939:Epitopes; D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I; D003173:Complement C1s