Grass-specific CD4+ T-cells exhibit varying degrees of cross-reactivity, implications for allergen-specific immunotherapy

• Published in: Clinical and experimental allergy Vol. 44; no. 7; pp. 986 - 998
• Main Authors: Archila, L. D., DeLong, J. H., Wambre, E., James, E. A., Robinson, D. M., Kwok, W. W.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.07.2014; Wiley Subscription Services, Inc
• Subjects: Alleles; Allergens - immunology; Allergies; allergy; Amino Acid Sequence; Antigens, Plant - chemistry; Antigens, Plant - immunology; Basophils - immunology; Basophils - metabolism; CD4; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cross Reactions - immunology; cross-reactivity; Cytokines - metabolism; Desensitization, Immunologic; epitopes; Epitopes, T-Lymphocyte - chemistry; Epitopes, T-Lymphocyte - immunology; grass-pollen; HLA Antigens - genetics; HLA Antigens - immunology; Humans; Immunoglobulin E - immunology; Immunotherapy; Lymphocyte Activation - immunology; Medical research; MHC class II tetramers; Peptides - chemistry; Peptides - immunology; Phleum pratense; Poaceae - immunology; Pollen - immunology; Pooideae; T-Cell Antigen Receptor Specificity - immunology; T-cells; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-cells; epitopes; CD4; MHC class II tetramers; allergy; cross-reactivity; Pooideae; grass-pollen
• ISSN: 0954-7894; 1365-2222; 1365-2222
• DOI: 10.1111/cea.12324

Summary 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.