Acv. Arnholdt et al., ANALYSIS AND PARTIAL EPITOPE MAPPING OF HUMAN T-CELL RESPONSES TO TRYPANOSOMA-CRUZI CYSTEINYL PROTEINASE, The Journal of immunology, 151(6), 1993, pp. 3171-3179
Human infection with Trypanosoma cruzi (Chagas' disease) is usually ac
companied by humoral and cellular immune responses to GP57/51, a major
antigen that was recently identified as a prominent cysteinyl protein
ase (cruzipain). The PBMC responses of 11 chronic chagasic patients an
d the properties of anti-cruzipain T cell lines are reported herein. G
P57/51, isolated from Y strain epimastigotes (n-cruzipain) or the reco
mbinant protein expressed in E. coli (r-cruzipain), elicited prolifera
tive responses of variable intensity from the patient's PBMC. T cell l
ines were then generated using each of these antigens. These lines, wh
ich always carried the CD4+ phenotype, were reciprocally stimulated by
n-cruzipain or r-cruzipain, the responses to the former being usually
stronger. The analysis of cytokine production suggested that Th1-like
subsets dominate the patient's responses: IFN-gamma was consistently
induced on stimulation with either n-cruzipain or r-cruzipain. In cont
rast, IL-4 was present in very small concentrations or was undetectabl
e. We then sought to define T cell epitopes of cruzipain using synthet
ic peptides spanning portions of the central (catalytic) domain and CO
OH-terminal extension. From a panel of 11 peptides, only one 33 mer pe
ptide (P214) elicited a strong proliferative response on anti-cruzipai
n T cell lines, the intensity being comparable to that induced by r-cr
uzipain. Conversely, T cell lines started with P214 were responsive to
either n-cruzipain or r-cruzipain, the proliferative responses again
being accompanied by IFN-gamma production, but not IL-4. Interestingly
, P214 is located in a conserved region of the catalytic domain of cru
zipain, hence may propitiate opportunities for cross-recognition of ot
her members of the papain superfamily. Fine epitope mapping should rev
eal whether structurally similar regions of host thiol-cathepsins can
be potential targets for cross-reactive T cell responses during chroni
c human infection.