Class II MHC/peptide complexes are released from APC and are acquired by T cell responders during specific antigen recognition.
T cell expression of class II MHC/peptide complexes may be important for maintenance of peripheral self-tolerance, but mechanisms underlying the genesis of class II MHC glycoproteins on T cells are not well resolved. T cell APC (T-APC) used herein were transformed IL-2-dependent clones that constitutively synthesized class II MHC glycoproteins. When pulsed with myelin basic protein (MBP) and injected into Lewis rats, these T-APC reduced the severity of experimental autoimmune encephalomyelitis, whereas unpulsed T-APC were without activity. Normal MBP-reactive clones cultured without APC did not express class II MHC even when activated with mitogens and exposed to IFN-gamma. However, during a 4-h culture with T-APC or macrophage APC, recognition of MBP or mitogenic activation of responder T cells elicited high levels of I-A and I-E expression on responders. Acquisition of class II MHC glycoproteins by responders was resistant to the protein synthesis inhibitor cycloheximide, coincided with transfer of a PKH26 lipophilic dye from APC to responders, and resulted in the expression of syngeneic and allogeneic MHC glycoproteins on responders. Unlike rested I-A- T cell clones, rat thymic and splenic T cells expressed readily detectable levels of class II MHC glycoproteins. When preactivated with mitogens, naive T cells acquired APC-derived MHC class II molecules and other membrane-associated proteins when cultured with xenogeneic APC in the absence of Ag. In conclusion, this study provides evidence that APC donate membrane-bound peptide/MHC complexes to Ag-specific T cell responders by a mechanism associated with the induction of tolerance.
Patel
D M
DM
Department of Microbiology and Immunology, East Carolina University School of Medicine, Greenville, NC 27858, USA.
Arnold
P Y
PY
White
G A
GA
Nardella
J P
JP
Mannie
M D
MD
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism*; D015478:Antigens, Heterophile / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D002461:Cell Line, Transformed / Q000637:transplantation; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism*; D006023:Glycoproteins / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000378:metabolism*; D007108:Immune Tolerance / Q000276:immunology; D007371:Interferon-gamma / Q000494:pharmacology; D007399:Interphase / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000494:pharmacology; D004676:Myelin Basic Protein / Q000276:immunology; D010455:Peptides / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000637:transplantation; D013950:Thymus Gland / Q000166:cytology
D015478:Antigens, Heterophile; D018984:Epitopes, T-Lymphocyte; D006023:Glycoproteins; D000949:Histocompatibility Antigens Class II; D008565:Membrane Proteins; D008934:Mitogens; D004676:Myelin Basic Protein; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma