T lymphocytes can recognize determinants unique to neuropeptides of guinea pig myelin basic protein containing a single D-isomer amino acid substitution.
The present studies were undertaken to examine how the substitution of racemized forms of selected amino acids in synthetic peptides of guinea pig myelin basic protein (GPMBP) would alter the host's immunological ability to recognize such molecules. Using peptides from the 69-84 sequence of GPMBP containing a D-serine at position 70 or 75 (69-84[D-ser70 or D-ser75]) or D-aspartate at position 82 (69-84[D-asp82]), the findings demonstrated that the position of the diastereomer substitution on these neuropeptides was critical with respect to the ability of the immune system to recognize the molecule. Thus substitution of D-asp at position 82 or D-ser at position 75 abrogated the ability of these peptides to induce experimental autoimmune encephalitis and proliferation of host T cells. In contrast, a peptide containing a D-ser70 residue was capable of inducing clinical disease in rats, as well as stimulating T lymphocytes from 69-84-(D-ser70)-injected animals. Moreover, although this D-peptide was shown to share at least some determinant(s) with the 69-84 peptide, the use of 69-84(D-ser70)-stimulated cell lines demonstrated that some epitope(s) unique to this molecule could stimulate CD4+ syngeneic T cells.
Department of Microbiology and Immunology, University of Miami School of Medicine, FL 33101.
R B
RB
Levy
S
S
Miller
N M
NM
Garcia
M
M
Jones
G H
GH
Fisher
E H
EH
Man
D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D005260:Female; D008213:Lymphocyte Activation / Q000187:drug effects; D004676:Myelin Basic Protein / Q000276:immunology*; D009479:Neuropeptides / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology*
D000939:Epitopes; D004676:Myelin Basic Protein; D009479:Neuropeptides