T cell recognition of major histocompatibility complex class II complexes with invariant chain processing intermediates.
Peptides from the lumenal portion of invariant chain (Ii) spanning residues 80-106 (class II-associated Ii peptide [CLIP]) are found in association with several mouse and human major histocompatibility complex (MHC) class II allelic variants in wild-type and presentation-deficient mutant cells. The ready detection of these complexes suggests that such an intermediate is essential to the MHC class II processing pathway. In this study, we demonstrate that T cells recognize CLIP/MHC class II complexes on the surface of normal and mutant cells in a manner indistinguishable from that of nominal antigenic peptides. Surprisingly, T cell hybrids specific for human CLIP bound to murine MHC class II molecule I-Ab and a new monoclonal antibody 30-2 with the same specificity, recognize two independent epitopes expressed on this peptide/class II complex. T cell recognition is dependent on a Gln residue (position 100) in CLIP, whereas the 30-2 antibody recognizes a Lys residue-at position 90. These two residues flank the 91-99 sequence that is conserved among human, mouse, and rat Ii, potentially representing an MHC class II-binding site. Our results suggest that the COOH-terminal portion of CLIP that includes TCR contact residue Gln 100 binds in the groove of I-Ab molecule. Moreover, both T cells and the antibody recognize I-Ab complexed with larger Ii processing intermediates such as the approximately 12-kD small leupeptin-induced protein (SLIP) fragments. Thus, SLIP fragments contain a CLIP region bound to MHC class II molecule in a conformation identical to that of a free CLIP peptide. Finally, our data suggest that SLIP/MHC class II complexes are precursors of CLIP/MHC class II complexes.
Morkowski
S
S
Department of Immunology, University of Washington, Seattle 98195, USA.
Goldrath
A W
AW
Eastman
S
S
Ramachandra
L
L
Freed
D C
DC
Whiteley
P
P
Rudensky AYu
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology; D001665:Binding Sites; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D005998:Glycine; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D006822:Hybrid Cells; D007976:Leupeptins / Q000378:metabolism; D008239:Lysine; D046911:Macromolecular Substances; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D000944:Antigens, Differentiation, B-Lymphocyte; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D007976:Leupeptins; D046911:Macromolecular Substances; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; C045084:invariant chain; C032854:leupeptin; D008239:Lysine; D005998:Glycine