PMID- 24708411 OWN - NLM STAT- MEDLINE DCOM- 20150303 LR - 20211021 IS - 1365-2222 (Electronic) IS - 0954-7894 (Print) IS - 0954-7894 (Linking) VI - 44 IP - 7 DP - 2014 Jul TI - Grass-specific CD4(+) T-cells exhibit varying degrees of cross-reactivity, implications for allergen-specific immunotherapy. PG - 986-98 LID - 10.1111/cea.12324 [doi] AB - BACKGROUND: Conceptually, allergic responses may involve cross-reactivity by antibodies or T-cells. While IgE cross-reactivity among grass-pollen allergens has been observed, cross-reactivity at the allergen-specific T-cell level has been less documented. Identification of the patterns of cross-reactivity may improve our understanding, allowing optimization of better immunotherapy strategies. OBJECTIVES: We use Phleum pratense as model for the studying of cross-reactivity at the allergen-specific CD4(+) T cell level among DR04:01 restricted Pooideae grass-pollen T-cell epitopes. METHODS: After in vitro culture of blood mono-nucleated cells from grass-pollen-allergic subjects with specific Pooideae antigenic epitopes, dual tetramer staining with APC-labelled DR04:01/Phleum pratense tetramers and PE-labelled DR04:01/Pooideae grass homolog tetramers was assessed to identify cross-reactivity among allergen-specific DR04:01-restricted T-cells in six subjects. Direct ex vivo staining enabled the comparison of frequency and phenotype of different Pooideae grass-pollen reactive T-cells. Intracellular cytokine staining (ICS) assays were also used to examine phenotypes of these T-cells. RESULTS: T-cells with various degrees of cross-reactive profiles could be detected. Poa p 1 97-116 , Lol p 1 221-240 , Lol p 5a 199-218 , and Poa p 5a 199-218 were identified as minimally cross-reactive T-cell epitopes that do not show cross-reactivity to Phl p 1 and Phl p 5a epitopes. Ex vivo tetramer staining assays demonstrated T-cells that recognized these minimally cross-reactive T-cell epitopes are present in Grass-pollen-allergic subjects. CONCLUSIONS: Our results suggest that not all Pooideae grass epitopes with sequence homology are cross-reactive. Non-cross-reactive T-cells with comparable frequency, phenotype and functionality to Phl p-specific T-cells suggest that a multiple allergen system should be considered for immunotherapy instead of a mono-allergen system. CI - (c) 2014 John Wiley & Sons Ltd. FAU - Archila, L D AU - Archila LD AD - Benaroya Research Institute at Virginia Mason, Seattle, WA, USA. FAU - DeLong, J H AU - DeLong JH FAU - Wambre, E AU - Wambre E FAU - James, E A AU - James EA FAU - Robinson, D M AU - Robinson DM FAU - Kwok, W W AU - Kwok WW LA - eng GR - HHSN272200700046C/AI/NIAID NIH HHS/United States GR - R01 AI095074/AI/NIAID NIH HHS/United States GR - 5 R01 AI095074/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - England TA - Clin Exp Allergy JT - Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology JID - 8906443 RN - 0 (Allergens) RN - 0 (Antigens, Plant) RN - 0 (Cytokines) RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (HLA Antigens) RN - 0 (Peptides) RN - 37341-29-0 (Immunoglobulin E) SB - IM CIN - Clin Exp Allergy. 2014 Jul;44(7):898-900. PMID: 24953633 MH - Alleles MH - Allergens/*immunology MH - Amino Acid Sequence MH - Antigens, Plant/chemistry/immunology MH - Basophils/immunology/metabolism MH - CD4-Positive T-Lymphocytes/*immunology/metabolism MH - Cross Reactions/*immunology MH - Cytokines/metabolism MH - *Desensitization, Immunologic MH - Epitopes, T-Lymphocyte/chemistry/immunology MH - HLA Antigens/genetics/immunology MH - Humans MH - Immunoglobulin E/immunology MH - Lymphocyte Activation/immunology MH - Peptides/chemistry/immunology MH - Poaceae/*immunology MH - Pollen/immunology MH - T-Cell Antigen Receptor Specificity/immunology MH - T-Lymphocyte Subsets/*immunology/metabolism PMC - PMC4069242 MID - NIHMS583566 OTO - NOTNLM OT - CD4+ OT - MHC class II tetramers OT - Pooideae OT - T-cells OT - allergy OT - cross-reactivity OT - epitopes OT - grass-pollen EDAT- 2014/04/09 06:00 MHDA- 2015/03/04 06:00 PMCR- 2015/07/01 CRDT- 2014/04/09 06:00 PHST- 2013/12/03 00:00 [received] PHST- 2014/03/07 00:00 [revised] PHST- 2014/03/21 00:00 [accepted] PHST- 2014/04/09 06:00 [entrez] PHST- 2014/04/09 06:00 [pubmed] PHST- 2015/03/04 06:00 [medline] PHST- 2015/07/01 00:00 [pmc-release] AID - 10.1111/cea.12324 [doi] PST - ppublish SO - Clin Exp Allergy. 2014 Jul;44(7):986-98. doi: 10.1111/cea.12324.