Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
10
|
| pubmed:dateCreated |
1994-11-7
|
| pubmed:abstractText |
The functional status (Th1- versus Th2-like) of CD4 T cells primed against human collagen type IV (hCol IV) or a single 30mer peptide from the alpha 2 chain of this molecule is predicted by the major histocompatibility complex (MHC) class II (I-A) genotype of the responding mice. H-2s mice elicit Th1-like cell-mediated responses to these antigens, whereas Th2-like humoral responses are primed in H-2b,d,k mice. We now report that the ability of MHC to dictate T helper function in this system depends upon a single amino acid of the minimal alpha 2(IV) peptide. The C terminus of this minimal (12mer) peptide is -G-G-P-K, which is predicted to form a beta-turn. The present data demonstrate that the terminal lysine (K) stabilizes the immunogens full biological effects necessary for exclusive cell-mediated responses in H-2s mice. The lysine-truncated (11mer) peptide with otherwise identical sequence effectively primes T helper function in both H-2b and H-2s genotypes. Most importantly, our direct analysis of these peptides' presentation by live antigen-presenting cells (APC) reveals that the 12mer is bound at a log higher density on H-2s APC than on H-2b APC, and that the 11mer is presented at an equally low relative density on APC from both genotypes. In vitro analyses of 12mer/11mer cross-reactive Th clones demonstrate that I-As restricted clones require about 1-2 log lower doses of 12mer peptide than 11mer peptide to stimulate equivalent thymidine incorporation and cytokine release. By contrast, I-Ab-restricted (12mer/11mer cross-reactive) Th clones show no preference for the 12mer and require relatively high peptide doses similar to those required to stimulate the I-As clones with the 11mer peptide. Thus, the peptide dose requirements of Th clones reflect the high density of presentation associated with the 12mer: I-As ligand. Taken together, the results directly support the role of ligand density as an important control point in the functional decision of CD4 T cells.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Oct
|
| pubmed:issn |
0014-2980
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
24
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
2337-44
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:7925562-Amino Acid Sequence,
pubmed-meshheading:7925562-Animals,
pubmed-meshheading:7925562-Antigen-Presenting Cells,
pubmed-meshheading:7925562-CD4-Positive T-Lymphocytes,
pubmed-meshheading:7925562-Collagen,
pubmed-meshheading:7925562-Dose-Response Relationship, Immunologic,
pubmed-meshheading:7925562-Female,
pubmed-meshheading:7925562-H-2 Antigens,
pubmed-meshheading:7925562-Histocompatibility Antigens Class II,
pubmed-meshheading:7925562-Lymphocyte Activation,
pubmed-meshheading:7925562-Major Histocompatibility Complex,
pubmed-meshheading:7925562-Male,
pubmed-meshheading:7925562-Mice,
pubmed-meshheading:7925562-Mice, Inbred A,
pubmed-meshheading:7925562-Mice, Inbred C57BL,
pubmed-meshheading:7925562-Molecular Sequence Data,
pubmed-meshheading:7925562-Peptides,
pubmed-meshheading:7925562-Protein Structure, Secondary,
pubmed-meshheading:7925562-T-Lymphocytes, Helper-Inducer
|
| pubmed:year |
1994
|
| pubmed:articleTitle |
Major histocompatibility complex regulation of T helper functions mapped to a peptide C terminus that controls ligand density.
|
| pubmed:affiliation |
Division of Biology, Kansas State University, Manhattan 66506.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
|