Two distinct class II molecules encoded by the genes within HLA-DR subregion of HLA-Dw2 and Dw12 can act as stimulating and restriction molecules.
By using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), we investigated the difference in the HLA class II molecule between HLA-Dw2 and Dw12, both of which are typed as HLA-DR2 serologically. The anti-HLA-DR framework monoclonal antibody (MoAb) HU-4 precipitated an alpha-chain and two beta-chains of human class II molecules from both Dw2 and Dw12 homozygous B lymphoblastoid cell lines. It was demonstrated clearly that an alpha-chain (alpha 1) and one of the beta-chains (beta 1) showed no difference in mobility in the 2D-PAGE between Dw2 and Dw12, but that another beta chain (beta 2) of Dw2 was distinct from that of Dw12 in the 2D-PAGE profile. Thus, MoAb HU-4 precipitated alpha 1 beta 1 and alpha 1 beta 2 molecules from Dw2 and Dw12, and the alpha 1 beta 1 molecule appears to be an HLA-DR2 molecule. The alpha 1 beta 2 molecule, on the other hand, is a class II molecule distinct from those precipitated with anti-DR2, anti-DQw1 (DC1, MB1, MT1), or anti-FA MoAbs. MoAb HU-4 completely inhibited the mixed lymphocyte culture reaction (MLR) between Dw2 and Dw12, but anti-DR2 MoAb HU-30, which reacts only with the alpha 1 beta 1 molecule, did not show an inhibitory effect on the MLR between Dw2 and Dw12. The alpha 1 beta 2 molecule is therefore the molecule which elicits MLR between Dw2 and Dw12. An IL 2-dependent T cell line established from an HLA-Dw12/D blank heterozygous high responder to the streptococcal cell wall antigen (SCW) clearly distinguished the Dw2 specificity from Dw12 specificity expressed on the antigen-presenting cell (APC). Moreover, MoAb HU-4 markedly inhibited the cooperation between the T cell line and APC to respond to SCW. These observations indicate that the alpha 1 beta 2 molecule is recognized as a restriction molecule by the T cell line at the antigen presentation of SCW through APC MoAb HU-30 on the other hand partially inhibited the MLR between Dw2 or Dw12 homozygous cell as a stimulator cell and non DR2 cell as a responder cell. It markedly inhibited the proliferative response of the Dw12/D- heterozygous T cell line to SCW, presented by Dw2+ but Dw12- allogeneic APC, and the peripheral response of Dw2 or Dw12 homozygous peripheral blood lymphocytes to SCW. Thus, two distinct class II molecules encoded by the genes within the HLA-DR subregion of HLA-Dw2 and Dw12 can act as stimulating molecules in the MLR and as restriction molecules in the antigen presentation by APC.
Sone
T
T
Tsukamoto
K
K
Hirayama
K
K
Nishimura
Y
Y
Takenouchi
T
T
Aizawa
M
M
Sasazuki
T
T
D000911:Antibodies, Monoclonal / Q000502:physiology; D000938:Antigen-Presenting Cells / Q000276:immunology; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D005802:Genes, MHC Class II; D006681:HLA-D Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D015802:HLA-DR2 Antigen; D000949:Histocompatibility Antigens Class II / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed / Q000379:methods; D011233:Precipitin Tests; D013291:Streptococcus / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D006681:HLA-D Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D015802:HLA-DR2 Antigen; C039901:HLA-Dw12 antigens; D000949:Histocompatibility Antigens Class II