HLA Class I-T cell epitopes from trans-sialidase proteins reveal functionally distinct subsets of CD8+ T cells in chronic Chagas disease.
BACKGROUND
Previously, we identified a set of HLA-A020.1-restricted trans-sialidase peptides as targets of CD8+ T cell responses in HLA-A0201+ individuals chronically infected by T. cruzi.


RESULTS
Herein, we report the identification of peptides encoded by the same trans-sialidase gene family that bind alleles representative of the 6 most common class I HLA-supertypes. Based on a combination of bioinformatic predictions and HLA-supertype considerations, a total of 1001 epitopes predicted to bind to HLA A01, A02, A03, A24, B7 and B44 supertypes was selected. Ninety-six supertype-binder epitopes encoded by multiple trans-sialidase genes were tested for the ability to stimulate a recall CD8+ T cell response in the peripheral blood from subjects with chronic T. cruzi infection regardless the HLA haplotype. An overall hierarchy of antigenicity was apparent, with the A02 supertype peptides being the most frequently recognized in the Chagas disease population followed by the A03 and the A24 supertype epitopes. CD8+ T cell responses to promiscuous epitopes revealed that the CD8+ T cell compartment specific for T. cruzi displays a functional profile with T cells secreting interferon-gamma alone as the predominant pattern and very low prevalence of single IL-2-secreting or dual IFN-gamma/IL-2 secreting T cells denoting a lack of polyfunctional cytokine responses in chronic T. cruzi infection.


CONCLUSIONS
This study identifies a set of T. cruzi peptides that should prove useful for monitoring immune competence and changes in infection and disease status in individuals with chronic Chagas disease.
Alvarez
María G
MG
Hospital Interzonal General de Agudos "Eva Perón", San Martín, Provincia de Buenos Aires, Argentina.
Postan
Miriam
M
Weatherly
D Brent
DB
Albareda
María C
MC
Sidney
John
J
Sette
Alessandro
A
Olivera
Carina
C
Armenti
Alejandro H
AH
Tarleton
Rick L
RL
Laucella
Susana A
SA
D000328:Adult; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002489:Central America / Q000453:epidemiology; D014355:Chagas Disease / Q000453:epidemiology / Q000235:genetics / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte / Q000235:genetics* / Q000276:immunology; D006023:Glycoproteins / Q000235:genetics*; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D015234:HLA-A Antigens / Q000235:genetics; D015789:HLA-A2 Antigen; D015235:HLA-B Antigens / Q000276:immunology; D006384:Hemagglutination; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D008875:Middle Aged; D009439:Neuraminidase / Q000235:genetics*; D013020:South America / Q000453:epidemiology; D013601:T-Lymphocytes / Q000276:immunology; D014349:Trypanosoma cruzi / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D006023:Glycoproteins; D006680:HLA Antigens; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D015235:HLA-B Antigens; D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma; C069715:trans-sialidase; D009439:Neuraminidase