Human CD4+ T Cell Responses to the Dog Major Allergen Can f 1 and Its Human Homologue Tear Lipocalin Resemble Each Other

Abstract

Lipocalin allergens form a notable group of proteins, as they contain most of the significant respiratory allergens from mammals. The basis for the allergenic capacity of allergens in the lipocalin family, that is, the development of T-helper type 2 immunity against them, is still unresolved. As immunogenicity has been proposed to be a decisive feature of allergens, the purpose of this work was to examine human CD4+ T cell responses to the major dog allergen Can f 1 and to compare them with those to its human homologue, tear lipocalin (TL). For this, specific T cell lines were induced in vitro from the peripheral blood mononuclear cells of Can f 1-allergic and healthy dog dust-exposed subjects with peptides containing the immunodominant T cell epitopes of Can f 1 and the corresponding TL peptides. We found that the frequency of Can f 1 and TL-specific T cells in both subject groups was low and close to each other, the difference being about two-fold. Importantly, we found that the proliferative responses of both Can f 1 and TL-specific T cell lines from allergic subjects were stronger than those from healthy subjects, but that the strength of the responses within the subject groups did not differ between these two antigens. Moreover, the phenotype of the Can f 1 and TL-specific T cell lines, determined by cytokine production and expression of cell surface markers, resembled each other. The HLA system appeared to have a minimal role in explaining the allergenicity of Can f 1, as the allergic and healthy subjects' HLA background did not differ, and HLA binding was very similar between Can f 1 and TL peptides. Along with existing data on lipocalin allergens, we conclude that strong antigenicity is not decisive for the allergenicity of Can f 1.

Allergenic Can f 1 and its human homologue Lcn‐1 direct dendritic cells to induce divergent immune responses

“…These homologous lipocalins showed similar results like Lcn-1 and Can f 1 regarding the induction of IL-12 and T-helper cell subtypes ( Fig. 5) and Liukko et al [38] show that lipocalin derived peptides alone are not able to drive differential immune responses which supports our view that the interaction of lipocalins with DCs is essential to define the type of immune response. More studies might be necessary to clear these discrepancies.…”

“…Although most of the data shown in these reports are not directly comparable to our study, some are still contradictory. Virtanen and colleagues found that mammalian lipocalin allergens do not exhibit DC-activating capacity and found no differences in the CD4 + T cell responses to the two homologous lipocalins 38,39 while Preston et al . 40 found immunomodulatory activity of hard tick-derived lipocalins and Roth-Walter et al .…”

“…Although most of the data shown in these reports are not directly comparable to our study, some are still contradictory. Virtanen and colleagues found that mammalian lipocalin allergens do not exhibit DC-activating capacity and found no differences in the CD4 + T cell responses to the two homologous lipocalins [38,39] while Preston et al [40] found immunomodulatory activity of hard tick-derived lipocalins and Roth-Walter et al found that the lipocalin cow allergen holo-Bos d 5 and the lipocalin-like holo-Bet v2 promote Th2 cells [41,42]. In our study we confirm DC-modulatory activity by a second pair of homologous lipocalins, the cat dander allergen Fel d 4 and its putative human homologue MUP.…”

Human Saliva Acting as an Allergen

“…Recent studies have shown that human CD4+ T cell responses are similar to both the major dog allergen Can f 1 and its human homologue tear lipocalin [7]. Bites from rodents can also cause anaphylaxis.…”

Structural similarities of human and mammalian lipocalins, and their function in innate immunity and allergy

“…T‐cell responses have been found to be ‘suboptimal’ for Can f 1 , although resembling those to human LCN1 . Can f 4 T‐cell responses were shown to be a Th2‐deviated memory response, in part to peptides with promiscuous HLA‐binding capacity , whereas the DR4–DQ8 haplotype and T‐cell receptor Vbeta T‐cell subset were indicative for the absence of Can f 1 allergy .…”