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T cell recognition of major histocompatibility complex class II complexes with invariant chain processing
S Morkowski1, A W Goldrath, S Eastman
1Department of Immunology, University of Washington, Seattle 98195, USA.
The Journal of Experimental Medicine
|November 1, 1995
Summary
T cells recognize major histocompatibility complex (MHC) class II-associated invariant chain peptides (CLIP) bound to MHC class II molecules. These CLIP/MHC class II complexes are essential intermediates in antigen processing and presentation.
Area of Science:
- Immunology
- Molecular Biology
Background:
- Invariant chain (Ii) peptides, specifically class II-associated Ii peptide (CLIP), are found associated with major histocompatibility complex (MHC) class II molecules.
- These CLIP/MHC class II complexes are crucial intermediates in the MHC class II antigen processing and presentation pathway.
Purpose of the Study:
- To investigate T cell recognition of CLIP/MHC class II complexes.
- To determine the structural basis for T cell and antibody recognition of these complexes.
- To explore the role of larger invariant chain processing intermediates in MHC class II presentation.
Main Methods:
- Utilized T cell hybridoma technology to assess T cell recognition of CLIP/MHC class II complexes.
- Employed monoclonal antibodies to identify specific epitopes on the CLIP/MHC class II complex.
- Analyzed the binding of T cells and antibodies to complexes formed with different invariant chain processing intermediates.
Main Results:
- T cells recognize CLIP/MHC class II complexes similarly to nominal antigenic peptides.
- T cell recognition of the human CLIP/murine I-Ab complex is dependent on a Gln residue at position 100 in CLIP.
- A monoclonal antibody (30-2) recognizes a Lys residue at position 90, indicating distinct epitopes.
- Larger invariant chain processing intermediates, such as SLIP fragments, form complexes with MHC class II that are recognized by T cells and antibodies, mimicking free CLIP/MHC class II complexes.
- SLIP/MHC class II complexes appear to be precursors to CLIP/MHC class II complexes.
Conclusions:
- T cells and antibodies can recognize CLIP/MHC class II complexes, highlighting their role in immune surveillance.
- Specific residues within CLIP (Gln 100 for T cells, Lys 90 for antibody 30-2) are critical for recognition.
- Invariant chain processing intermediates like SLIP fragments present CLIP in a conformationally relevant manner for MHC class II presentation.
- These findings elucidate key steps in the MHC class II antigen processing pathway and the nature of immune recognition of these intermediates.