Abrogation of H-2-restricted CTL responses and efficient recognition of HLA-A3 molecules in DBA/2 HLA/A24 responder mice.
DBA/2 (H-2d) HLA-B7 x human beta 2-microglobulin transgenic and DBA/2 nontransgenic mice stimulated by DBA/2 HLA-A3 x human beta 2-microglobulin transgenic mouse spleen cells developed potent H-2Kd restricted cytolytic responses with recognition of a peptide from the second domain of the HLA-A3 H chain. These H-2Kd-restricted responses obliterated, as a rule, cytolytic responses with direct recognition of the HLA-A3 molecules, even in HLA-B7 transgenic mice. These immunodominant H-2Kd-restricted responses could be abrogated in DBA/2 HLA-A24 mice because of cross-tolerance, the HLA-A3 derived-H-2Kd presented peptide being shared by several (including A24) HLA class I H chain allelic variants. Under such experimental circumstances, strong CTL responses with exclusive direct recognition of HLA-A3 molecules constantly developed. Further analysis of these responses in six DBA/2 HLA-A24 responder mice indicated that a large fraction of the mouse V beta and V alpha genes could be used to mount such CTL responses. Thus, by combining classical HLA class I transgenesis and selective destruction of H-2K and H-2D genes, it should be possible to derive useful strains of mice for the study of HLA class I-restricted CTL responses.
Barra
C
C
Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, Marseille, France.
Gournier
H
H
Garcia
Z
Z
Marche
P N
PN
Jouvin-Marche
E
E
Briand
P
P
Fillipi
P
P
Lemonnier
F A
FA
D000818:Animals; D001483:Base Sequence; D006183:H-2 Antigens / Q000235:genetics* / Q000276:immunology; D015234:HLA-A Antigens / Q000276:immunology*; D059871:HLA-A24 Antigen; D015791:HLA-A3 Antigen / Q000276:immunology*; D015793:HLA-B7 Antigen / Q000235:genetics; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D012313:RNA / Q000032:analysis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D001613:beta 2-Microglobulin / Q000235:genetics
D006183:H-2 Antigens; D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; D015791:HLA-A3 Antigen; D015793:HLA-B7 Antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta; D001613:beta 2-Microglobulin; D012313:RNA