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
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.