PMID- 21084459 OWN - NLM STAT- MEDLINE DCOM- 20110421 LR - 20240503 IS - 1556-679X (Electronic) IS - 1556-6811 (Print) IS - 1556-679X (Linking) VI - 18 IP - 1 DP - 2011 Jan TI - Human leukocyte antigens A*3001 and A*3002 show distinct peptide-binding patterns of the Mycobacterium tuberculosis protein TB10.4: consequences for immune recognition. PG - 125-34 LID - 10.1128/CVI.00302-10 [doi] AB - High-tuberculosis (TB)-burden countries are located in sub-Saharan Africa. We examined the frequency of human leukocyte antigen (HLA) alleles, followed by recombinant expression of the most frequent HLA-A alleles, i.e., HLA-A*3001 and HLA-A*3002, to study differences in mycobacterial peptide presentation and CD8(+) T-cell recognition. We screened a peptide library (9-mer peptides with an 8-amino-acid overlap) for binding, affinity, and off-rate of the Mycobacterium tuberculosis-associated antigen TB10.4 and identified only three TB10.4 peptides with considerable binding to HLA-A*3001. In contrast, 22 peptides bound to HLA-A*3002. This reflects a marked difference in the binding preference between the two alleles, with A*3002 tolerating a more promiscuous peptide-binding pattern and A*3001 accommodating only a very selective peptide repertoire. Subsequent analysis of the affinity and off-rate of the binding peptides revealed a strong affinity (8 nM to 7 muM) and moderate off-rate (20 min to 3 h) for both alleles. Construction of HLA-A*3001 and HLA-A*3002 tetramers containing selected binding peptides from TB10.4, including a peptide which was shared among both alleles, QIMYNYPAM (TB10.4(3-11)), allowed us to enumerate epitope-specific T cells in HLA-A*3001- and HLA-A*3002-typed patients with active TB. HLA-A*3001 and HLA-A*3002 major histocompatibility complex-peptide complexes were recognized in individuals with active TB, irrespective of their homozygous HLA-A*3001 or HLA-A*3002 genetic background. The antigen-specific T cells exhibited the CD45RA(+) CCR7(+) precursor phenotype and the interleukin-7 receptor (CD127), which were different from the phenotype and receptor exhibited by the parental CD8(+) T-cell population. FAU - Axelsson-Robertson, Rebecca AU - Axelsson-Robertson R AD - Department of Microbiology and Tumor Cell Biology, Karolinska Institutet, Nobels Vag 18, Stockholm SE-171 82, Sweden. FAU - Ahmed, Raija K AU - Ahmed RK FAU - Weichold, Frank F AU - Weichold FF FAU - Ehlers, Marthie M AU - Ehlers MM FAU - Kock, Marleen M AU - Kock MM FAU - Sizemore, Donata AU - Sizemore D FAU - Sadoff, Jerry AU - Sadoff J FAU - Maeurer, Markus AU - Maeurer M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20101117 PL - United States TA - Clin Vaccine Immunol JT - Clinical and vaccine immunology : CVI JID - 101252125 RN - 0 (Antigens, Bacterial) RN - 0 (Epitopes) RN - 0 (HLA Antigens) RN - 0 (HLA-A Antigens) RN - 0 (HLA-A*30:01 antigen) RN - 0 (Peptide Library) RN - 0 (Peptides) RN - 0 (TB10.4 antigen, Mycobacterium tuberculosis) SB - IM MH - Amino Acid Sequence MH - Antigens, Bacterial/*chemistry/genetics/*immunology/metabolism MH - Binding Sites MH - CD8-Positive T-Lymphocytes/immunology MH - Epitopes/genetics/immunology MH - HLA Antigens/chemistry/genetics/*immunology/metabolism MH - HLA-A Antigens/chemistry/genetics/*immunology/metabolism MH - Humans MH - Molecular Sequence Data MH - Mycobacterium tuberculosis MH - Peptide Library MH - Peptides/chemistry/*immunology/metabolism MH - Protein Binding MH - South Africa MH - Tuberculosis, Pulmonary/immunology PMC - PMC3019778 EDAT- 2010/11/19 06:00 MHDA- 2011/04/22 06:00 PMCR- 2011/07/01 CRDT- 2010/11/19 06:00 PHST- 2010/11/19 06:00 [entrez] PHST- 2010/11/19 06:00 [pubmed] PHST- 2011/04/22 06:00 [medline] PHST- 2011/07/01 00:00 [pmc-release] AID - CVI.00302-10 [pii] AID - 0302-10 [pii] AID - 10.1128/CVI.00302-10 [doi] PST - ppublish SO - Clin Vaccine Immunol. 2011 Jan;18(1):125-34. doi: 10.1128/CVI.00302-10. Epub 2010 Nov 17.