[Coreceptor function of CD4 in response to MHC class I molecule].
Specificity of T cell receptor (TCR) and its interaction with coreceptor molecules play decisive role in successful passing of T lymphocytes via check-points during their development and finally determine the efficiency of adaptive immunity. Genes encoding alpha- and beta-chains of TCR hybridoma 1D1 have been cloned. The hybridoma 1D1 was established by the fusion of BWZ.36CD8alpha cell line with CD8+ memory cells specific to MHC class I H-2Kb molecule. Exploiting retroviral transduction of thymoma 4G4 cells with TCR genes and coreceptors CD4 and CD8, variants of this cell line expressing on the surface CD3/TCR complex and coreceptors, separately or simultaneously have been obtained. The main function of CD4 is stabilization of interaction between TCR and MHC class II molecule. Nevertheless, we have found that CD4 could successfully participate in the activation of transfectants via TCR specific to MHC class I molecule H-2Kb. Moreover, coreceptor CD4 dominates CDS, because the response of transfectants CD4+CD8+ is blocked by antibodies to CD4 and MHC Class II Ab molecule but not to coreceptor CD8. The response of CD4+ cells was not due to cross-reaction between TCR 1D1 with MHC class II molecules, because transfectants do not respond to splenocytes of H-2b knockouted mice with impaired assembly of TCR/beta2-microglobulin/peptide complexes resulting in their absence on the cell surphace. The effect of domination was not due to sequestration of kinase p56lck, because truncated CD4 with the loss of binding motif for p56lck remained functional in 4G4 cells. Results obtained can explain the number of features of intrathymic selection and represent experimental basis for development of new methods of cancer gene therapy.
Zvezdova
E S
ES
Grinenko
T S
TS
Pobezinskaia
E L
EL
Pobezinskiĭ
L A
LA
Kazanskiĭ
D B
DB
D020816:Amino Acid Motifs / Q000276:immunology; D000818:Animals; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D006825:Hybridomas; D007156:Immunologic Memory / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*
D017252:CD3 Complex; D015704:CD4 Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)