Axelsson-Robertson, RebeccaAhmed, Raija K.Weichold, Frank F.Ehlers, Marthie MagdaleenKock, Marleen M.Sizemore, DonataSadoff, JerryMaeurer, Markus2011-02-182011-02-182011-01Axelsson-Robertson, R, Ahmed, RK, Weichold, FF, Ehlers, MM, Kock, MM, Sizemore, D, Sadoff, J & Maeurer, M 2010, 'Human leukocyte antigens A*3001 and A*3002 show distinct peptide-binding patterns of the Mycobacterium tuberculosis protein TB10.4: consequences for immune recognition', Clinical and Vaccine Immunology, vol. 18, no. 1, pp. 125–134. [http://cvi.asm.org/]1556-681110.1128/CVI.00302-10http://hdl.handle.net/2263/15867High-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 M) 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 (TB10.43–11), 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.en© 2011, American Society for Microbiology. All Rights Reserved.HumanLeukocyteAntigensPeptide-BindingMycobacterium tuberculosisArticle