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.
Article|
November 01 1995
T cell recognition of major histocompatibility complex class II complexes with invariant chain processing intermediates.
S Morkowski,
S Morkowski
Department of Immunology, University of Washington, Seattle 98195, USA.
Search for other works by this author on:
A W Goldrath,
A W Goldrath
Department of Immunology, University of Washington, Seattle 98195, USA.
Search for other works by this author on:
S Eastman,
S Eastman
Department of Immunology, University of Washington, Seattle 98195, USA.
Search for other works by this author on:
L Ramachandra,
L Ramachandra
Department of Immunology, University of Washington, Seattle 98195, USA.
Search for other works by this author on:
D C Freed,
D C Freed
Department of Immunology, University of Washington, Seattle 98195, USA.
Search for other works by this author on:
P Whiteley,
P Whiteley
Department of Immunology, University of Washington, Seattle 98195, USA.
Search for other works by this author on:
Rudensky AYu
Rudensky AYu
Department of Immunology, University of Washington, Seattle 98195, USA.
Search for other works by this author on:
S Morkowski
Department of Immunology, University of Washington, Seattle 98195, USA.
A W Goldrath
Department of Immunology, University of Washington, Seattle 98195, USA.
S Eastman
Department of Immunology, University of Washington, Seattle 98195, USA.
L Ramachandra
Department of Immunology, University of Washington, Seattle 98195, USA.
D C Freed
Department of Immunology, University of Washington, Seattle 98195, USA.
P Whiteley
Department of Immunology, University of Washington, Seattle 98195, USA.
Rudensky AYu
Department of Immunology, University of Washington, Seattle 98195, USA.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1995) 182 (5): 1403–1413.
Citation
S Morkowski, A W Goldrath, S Eastman, L Ramachandra, D C Freed, P Whiteley, Rudensky AYu; T cell recognition of major histocompatibility complex class II complexes with invariant chain processing intermediates.. J Exp Med 1 November 1995; 182 (5): 1403–1413. doi: https://doi.org/10.1084/jem.182.5.1403
Download citation file: