The association between murine beta 2-microglobulin and HLA class I heavy chains results in serologically detectable conformational changes of both chains.
HLA-A3-, HLA-B7-, and HLA-CW3-transfected L cells, maintained in medium supplemented with murine serum so as to ensure that the human heavy chains were associated with murine beta 2-microglobulin, were subjected to a systematic serologic analysis for an evaluation of the structural consequences of such an heterologous association. The hybrid molecules exhibited alterations of their serologic reactivities that suggest the occurrence of structural modifications of both light and heavy chains. Thus, reactivity of HLA-A3-, HLA-B7-, and HLA-Cw3-transfected L cells with a monoclonal antibody (B1.1G6) directed at a human beta 2-microglobulin specific antigenic determinant was observed; this implies structural modifications of murine beta 2-microglobulin after its association with HLA class I heavy chains. Conversely, a profound reduction of the reactivity of the same transfectants with a monoclonal antibody (W6/32) directed at a monomorphic heavy chain related epitope was observed. The W6/32 reactivity was restored after replacement of the murine by the human light chain, indicating that the conformation adopted by the HLA class I heavy chain depends on the origin of the beta 2-microglobulin associated. Therefore it appears that the complex interactions that develop between the extracellular domains (including the one formed by the light chain) markedly influence the overall structure and the antigenic properties of HLA class I molecules.
P
P
Ferrier
C
C
Layet
D H
DH
Caillol
B R
BR
Jordan
F A
FA
Lemonnier
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000937:Antigen-Antibody Reactions; D000939:Epitopes / Q000032:analysis / Q000235:genetics / Q000276:immunology; D006680:HLA Antigens / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D015791:HLA-A3 Antigen; D015793:HLA-B7 Antigen; D015236:HLA-C Antigens; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007739:L Cells / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008808:Mice, Inbred CBA; D011487:Protein Conformation; D014162:Transfection; D001613:beta 2-Microglobulin / Q000032:analysis* / Q000235:genetics / Q000276:immunology
D000911:Antibodies, Monoclonal; D000939:Epitopes; D006680:HLA Antigens; D015791:HLA-A3 Antigen; D015793:HLA-B7 Antigen; D015236:HLA-C Antigens; C038653:HLA-C*03 antigen; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D001613:beta 2-Microglobulin