| Reference | ||
|---|---|---|
| Reference Type | Literature | IEDB_Reference:1004898 |
| Title | Impact of MHC class I alleles on the M. tuberculosis antigen-specific CD8+ T-cell response in patients with pulmonary tuberculosis. | |
| Authors | F F Weichold; S Mueller; C Kortsik; W E Hitzler; M J Wulf; D M Hone; J C Sadoff; M J Maeurer | |
| Affiliations | Aeras Global TB Vaccine Foundation, Bethesda, MD, USA. | |
| Journal | Genes Immun | |
| Year | 2007 | |
| Abstract | Challenged by scattered understanding of protective immunity to Mycobacterium tuberculosis (MTB), we have mapped peptide epitopes to human leukocyte antigen (HLA)-A*0101, A*0201, A*1101, A*2402, B*0702, B*0801 and B*1501 of the secreted mycobacterial antigen Ag85B, a vaccine candidate that may be associated with immune protection. Affinity (ED(50)) and half-life (t(1/2), off-rate) analysis for individual peptide species on HLA-A and HLA-B molecules revealed binding ranges between 10(-3) and 10(-7) M. After selection of the best matches, major histocompatibility complex class I/peptide tetramer complexes were constructed to measure the CD8+ T-cell responses directly ex vivo in peripheral blood mononuclear cells (PBMC) derived from 57 patients with acute pulmonary tuberculosis. Three patterns of (allele-) specific CD8+ recognition were identified: (a). Focus on one dominant epitope with additional recognition of several subdominant T-cell epitopes (HLA-A*0301, A*2402, B*0801 and B*1501); (b). Co-dominant recognition of two distinct groups of peptides presented by HLA-B*0702; and (c). Diverse and broad recognition of peptides presented by HLA-A*0201. Peptides that bound with slow off-rates to class I alleles, that is HLA-A*0201, were associated with low frequency of CD8+ T cells in PBMCs from patients with tuberculosis. HLA-B alleles showed fast off-rates in peptide binding and restricted high numbers (up to 6%) of antigen-specific CD8+ T cells in patients with pulmonary tuberculosis. | |
| Curation Last Updated | 2023-08-18 20:22:37 | |
| Epitope | ||
|---|---|---|
| Epitope ID | 5623 | IEDB_epitope:5623 |
| Chemical Type | Linear peptide | |
| Linear Sequence | AVYLLDGLR | |
| Source Molecule Name | Antigen 85-B precursor (85B) (Extracellular alpha-antigen) (Antigen 85 complex B) (Ag85B) (Mycolyl transferase 85B) (Fibronectin-binding protein B) (30 kDa extracellular protein) | |
| Source Organism | Mycobacterium tuberculosis | |
| Starting Position | 75 | |
| Ending Position | 83 | |
| Epitope Reference Details | ||
|---|---|---|
| Epitope Structure Defines | Exact Epitope | |
| Epitope Name | MTB Ag85 35-43 | |
| Reference Starting Position | 35 | |
| Reference Ending Position | 43 | |
| Location of Data in Reference | Table 1 | |
| Immunization | ||
|---|---|---|
| Host Organism | Homo sapiens (human) | |
| 1st In Vivo Process | ||
|---|---|---|
| In Vivo Process Type | Occurrence of infectious disease | |
| Disease State | tuberculosis | |
| Disease Stage | Acute/Recent onset; | OGMS:0000094 |
| 1st Immunogen | ||
|---|---|---|
| Epitope Relation | Source Organism | |
| Object Type | Organism | |
| Organism | Mycobacterium tuberculosis | |
| Immunogen Details | ||
|---|---|---|
| Immunogen Reference Name | Mycobacterium tuberculosis | |
| Immunization Comments | ||
|---|---|---|
| Immunization Comments | PBMCs were collected from 57 MHC class I-typed individuals with active pulmonary tuberculosis. | |
| T Cell Assay | ||
|---|---|---|
| Qualitative Measurement | Positive | |
| Method/Technique | multimer/tetramer | |
| Measurement of | qualitative binding | |
| Measurement Details | ||
|---|---|---|
| Quantitative measurement | 0.65 | |
| Number of Subjects Tested | 16 | |
| Number of Subjects Responded | 16 | |
| Response Frequency (%) | 100 | |
| Effector Cells | ||
|---|---|---|
| Effector Cell Tissue Type | Blood | |
| Effector Cell Type | T cell CD8+ | |
| Effector Cell Culture Conditions | Direct Ex Vivo | |
| MHC Allele | ||
|---|---|---|
| MHC Allele Name | HLA-A*03:01 | |
| MHC Evidence Code | Single allele present | |
| Antigen | ||
|---|---|---|
| Epitope Relation | Epitope | |
| Chemical Type | Linear peptide | |
| Linear Sequence | AVYLLDGLR | |
| Source Molecule Name | Antigen 85-B precursor (85B) (Extracellular alpha-antigen) (Antigen 85 complex B) (Ag85B) (Mycolyl transferase 85B) (Fibronectin-binding protein B) (30 kDa extracellular protein) | |
| Source Organism | Mycobacterium tuberculosis | |
| Starting Position | 75 | |
| Ending Position | 83 | |
| Antigen Details | ||
|---|---|---|
| Antigen Reference Name | MTB Ag85 35-43 | |
| Assay Reference Details | ||
|---|---|---|
| Assay Comments by IEDB Curator | Tetramer-reactive T cells were observed in patients with active TB. The predominant class I response directed against Ag85B in TB patients is HLA-B (highest frequency of tetramer-reactive T cells). | |
| Location of Assay Data in Reference | Figure 3 | |