ASPECTS OF ANTIGEN MIMICRY REVEALED BY IMMUNIZATION WITH A PEPTIDE MIMETIC OF CRYPTOCOCCUS-NEOFORMANS POLYSACCHARIDE

Citation
P. Valadon et al., ASPECTS OF ANTIGEN MIMICRY REVEALED BY IMMUNIZATION WITH A PEPTIDE MIMETIC OF CRYPTOCOCCUS-NEOFORMANS POLYSACCHARIDE, The Journal of immunology (1950), 161(4), 1998, pp. 1829-1836
Citations number
25
Categorie Soggetti
Immunology
ISSN journal
00221767
Volume
161
Issue
4
Year of publication
1998
Pages
1829 - 1836
Database
ISI
SICI code
0022-1767(1998)161:4<1829:AOAMRB>2.0.ZU;2-M
Abstract
We have recently identified peptide mimetics of the Cryptococcus neofo rmans capsular polysaccharide by screening phage display peptide libra ries. 2H1, one of a large family of mAbs against the glucuronoxylomann an fraction (GXM), is highly protective and binds several peptide moti fs, This study analyzes the immunologic properties of P601E (SYSWMYE), a peptide from the low affinity motif (W/YXWM/LYE) that has an extend ed cross-reactivity among anti-GXM mAbs and whose binding correlates w ith the protective potential of mAbs in experimental infection. P601E is a mimetic, since it competes for GXM binding to 2H1, but not a mimo tope, since it does not elicit an anti-GXM response. Sequence analysis of 14 anti-P601E mAbs indicates that anti-P601E mAbs elicited in BALB /c mice have an order of homology with 2H1 of V kappa > J kappa >> V-H > J(H) > D. Further screening of a peptide library with anti-P601E mA bs isolated peptides having a motif almost identical to the peptide mo tif selected by 2H1, When these results are compared to the crystal st ructure of a related peptide in complex with 2H1, there is a clear cor relation between the ability to elicit V region components of 2H1 Ab a nd peptide association with the V region, suggesting that the complete ness of the fit in the binding site is an important driving force for mimicry. As a consequence, improving affinity of a mimetic for the Ab binding site seems to be the most logical way to insure that all of th e appropriate V region segments are elicited and that useful mimotopes are created.