Journal article
Polymorphism in the β Chain of IAq versus IAp Influences Presentation of Protein but Not Peptide Antigens
Cellular immunology, Vol.165(2), pp.202-210
10/1995
DOI: 10.1006/cimm.1995.1206
PMID: 7553884
Abstract
T cells play a critical role in the development of collagen-induced arthritis (CIA). Immunization with heterologous (chick) type II collageu (cII) results in chronic inflammation with progressive damage to the joints. The expression of specific MHC Class II αβ dimers, including IAq, is critical to induction of disease. The α chains of IAq and IAp are identical in sequence. The IAq and IAp β chains differ by only four amino acid residues: 85, 86, 88, and 89. However, mice of the H-2P haplotype are not susceptible to CIA. To examine the impact of these structural differences in IA molecules on T cell Ag recognition, we studied presentation of cII peptides and denatured cII by APCs obtained from H-2q and H-2p mice. We also assessed presentation of ovalbumin, myelin basic protein (MBP), and MBP peptides by these APC populations. H-2q APCs presented both peptides and proteins to our T cell hybrids. In contrast, APCs obtained from H-2p mice presented peptides, but were defective in the processing and/or presentation of protein Ags. We then altered pairs of the residues in IAq to those found in lip using site-directed mutagenesis and transfected these constructs into M 12.C3 B cells. All transfectants were able to present peptides, but those expressing IAp were unable to present protein Ags. The use of transfectants expressing hybrid molecules (residues 85 and 86 from IAp, 88 and 89 from IAq, or vice versa) allowed us to localize the region responsible for this defect to residues 85 and 86 of the β chain. The presence of IAp residues (glu and thr versus gly and val in IAq) at these sites severely compromised the capacity for protein presentation. Resistance to CIA in H-2p haplotype mice may be a reflection of the limited repertoire of epitopes to which these mice can respond relative to susceptible H-2q mice.
Details
- Title: Subtitle
- Polymorphism in the β Chain of IAq versus IAp Influences Presentation of Protein but Not Peptide Antigens
- Creators
- Laurie E LambertJennifer S BerlingSusan D ThompsonJonathan A HartonGail A BishopEdmund Choi
- Resource Type
- Journal article
- Publication Details
- Cellular immunology, Vol.165(2), pp.202-210
- DOI
- 10.1006/cimm.1995.1206
- PMID
- 7553884
- ISSN
- 0008-8749
- eISSN
- 1090-2163
- Language
- English
- Date published
- 10/1995
- Academic Unit
- Microbiology and Immunology; President
- Record Identifier
- 9984001148102771
Metrics
21 Record Views