PMID- 15208742
OWN - NLM
STAT- MEDLINE
DCOM- 20050112
LR  - 20240322
IS  - 1076-1551 (Print)
IS  - 1528-3658 (Electronic)
IS  - 1076-1551 (Linking)
VI  - 9
IP  - 9-12
DP  - 2003 Sep-Dec
TI  - In silico prediction of peptides binding to multiple HLA-DR molecules accurately 
      identifies immunodominant epitopes from gp43 of Paracoccidioides brasiliensis 
      frequently recognized in primary peripheral blood mononuclear cell responses from 
      sensitized individuals.
PG  - 209-19
AB  - One of the major drawbacks limiting the use of synthetic peptide vaccines in 
      genetically distinct populations is the fact that different epitopes are 
      recognized by T cells from individuals displaying distinct major 
      histocompatibility complex molecules. Immunization of mice with peptide (181-195) 
      from the immunodominant 43 kDa glycoprotein of Paracoccidioides brasiliensis 
      (gp43), the causative agent of Paracoccidioidomycosis (PCM), conferred protection 
      against infectious challenge by the fungus. To identify immunodominant and 
      potentially protective human T-cell epitopes in gp43, we used the TEPITOPE 
      algorithm to select peptide sequences that would most likely bind multiple HLA-DR 
      molecules and tested their recognition by T cells from sensitized individuals. 
      The 5 most promiscuous peptides were selected from the gp43 sequence and the 
      actual promiscuity of HLA binding was assessed by direct binding assays to 9 
      prevalent HLA-DR molecules. Synthetic peptides were tested in proliferation 
      assays with peripheral blood mononuclear cells (PBMC) from PCM patients after 
      chemotherapy and healthy controls. PBMC from 14 of 19 patients recognized at 
      least one of the promiscuous peptides, whereas none of the healthy controls 
      recognized the gp43 promiscuous peptides. Peptide gp43(180-194) was recognized by 
      53% of patients, whereas the other promiscuous gp43 peptides were recognized by 
      32% to 47% of patients. The frequency of peptide binding and peptide recognition 
      correlated with the promiscuity of HLA-DR binding, as determined by TEPITOPE 
      analysis. In silico prediction of promiscuous epitopes led to the identification 
      of naturally immunodominant epitopes recognized by PBMC from a significant 
      proportion of a genetically heterogeneous patient population exposed to P. 
      brasiliensis. The combination of several such epitopes may increase the frequency 
      of positive responses and allow the immunization of genetically distinct 
      populations.
FAU - Iwai, Leo Kei
AU  - Iwai LK
AD  - Laboratory of Immunology, Heart Institute (Incor), Millenium Institutes, Brazil.
FAU - Yoshida, Marcia
AU  - Yoshida M
FAU - Sidney, John
AU  - Sidney J
FAU - Shikanai-Yasuda, Maria Aparecida
AU  - Shikanai-Yasuda MA
FAU - Goldberg, Anna Carla
AU  - Goldberg AC
FAU - Juliano, Maria Aparecida
AU  - Juliano MA
FAU - Hammer, Jurgen
AU  - Hammer J
FAU - Juliano, Luiz
AU  - Juliano L
FAU - Sette, Alessandro
AU  - Sette A
FAU - Kalil, Jorge
AU  - Kalil J
FAU - Travassos, Luiz Rodolpho
AU  - Travassos LR
FAU - Cunha-Neto, Edecio
AU  - Cunha-Neto E
LA  - eng
GR  - N01AI95362/AI/NIAID NIH HHS/United States
GR  - HHSN266200400006C/HS/AHRQ HHS/United States
GR  - N01-AI-95362/AI/NIAID NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Mol Med
JT  - Molecular medicine (Cambridge, Mass.)
JID - 9501023
RN  - 0 (43 kDa protein, Paracoccidioides)
RN  - 0 (Antigens, Fungal)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Fungal Proteins)
RN  - 0 (Glycoproteins)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Immunodominant Epitopes)
RN  - 0 (Peptides)
SB  - IM
MH  - Algorithms
MH  - Antigens, Fungal/*immunology
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - Cell Division
MH  - Cohort Studies
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Epitopes, T-Lymphocyte
MH  - Fungal Proteins/*immunology
MH  - Glycoproteins/*immunology
MH  - HLA-DR Antigens/*immunology
MH  - Humans
MH  - Immunoblotting
MH  - *Immunodominant Epitopes
MH  - Leukocytes, Mononuclear/*immunology/physiology
MH  - Paracoccidioides/*immunology
MH  - Paracoccidioidomycosis/immunology/pathology
MH  - Peptides/immunology/*metabolism
MH  - Predictive Value of Tests
PMC - PMC1430984
EDAT- 2004/06/23 05:00
MHDA- 2005/01/13 09:00
PMCR- 2003/01/01
CRDT- 2004/06/23 05:00
PHST- 2004/06/23 05:00 [pubmed]
PHST- 2005/01/13 09:00 [medline]
PHST- 2004/06/23 05:00 [entrez]
PHST- 2003/01/01 00:00 [pmc-release]
AID - mol9p209 [pii]
PST - ppublish
SO  - Mol Med. 2003 Sep-Dec;9(9-12):209-19.