The carrier effect in the secondary response to hapten‐protein conjugates. I. Measurement of the effect with transferred cells and objections to the local environment hypothesis

Abstract

objections to the local environment hypothesisA carrier effect is obtained typically when a hapten-protein conjugate is injected into an animal which has previously been primed with the same hapten conjugated to another carrier protein. Under these circumstances the antihapten secondary response is usually less than that which would have been obtained had the animal been injected with a conjugate prepared with the same carrier as that originally used for priming. Attempts have been made to account for the phenomenon in terms of the local environment hypothesis, which assumes that the receptor on immunologically competent cells recognises the hapten jointly with the area on the complete antigen which surrounds it. Alternatively the phenomenon can be accounted for by the hypothesis of cooperation, which assumes that the antigen is recognised by two receptors, one directed to the hapten and the other to a determinant on the carrier protein.Methods are described which enable carrier effects to be studied quantitatively

Cell-to-Cell Interaction in the Immune Response

“…Only then could collaboration take place. The ability of irradiated recipients of spleen cells from HGG.NIP-primed mice and of F~G.NIP-coated B cells to produce a substantial anti-NIP response (Table XIV) provides another example of overriding of the carrier effect (34). In the present model, overriding occurred only in the presence of T cells since anti-0 serum treatment of spleen cells from HGG.NIP-primed mice abrogated the response.…”

NK T cells provide lipid antigen-specific cognate help for B cells

“…We used a model hapten lipid antigen very similar to the well established haptenatedprotein antigen used by many investigators to decipher the nature of CD4 ϩ T cell help for protein-specific B cells (18). By measuring B cell responses against a CD1d-presented iNK T cell-restricted lipid ligand (␣GalCer) linked to the hapten NP, we determined the mechanisms of class-switched antigen-specific responses that require both BCR cross-linking by the hapten-bearing lipid antigen and T cell help provided by TCR-activated, CD1d-restricted iNK T cells.…”

“…Here, we use haptenated model lipid antigens to understand iNK T cell antilipid help for lipid specific B cells, mimicking the approach used to characterize CD4 ϩ T cell help for protein-specific B cells (18). We demonstrate cognate CD1d-restricted iNK T cell help for B cell proliferation and antibody production against the model haptened-lipid antigen.…”

Translating Molecular Insights in Autoimmunity into Effective Therapy

“…On the way, I visited Avrion (Av) Mitchison and Gerald Edelman and compared which lab might be more suitable for me. Av was a most charming host, inviting me to stay in his house and give a talk to his colleagues at the National Institute of Medical Research (NIMR) at Mill Hill, where there was a wonderful intellectual and friendly atmosphere (e.g., 26,27 It was an exciting place to be, rich in intellectual resources and modern scientific equipment, with Av's friendship with the Herzenbergs securing him one of the very first fluorescence-activated cell sorters (FACS) (28). Scientific visitors abounded, to give seminars in the crowded, small seminar room in the Department of Zoology, with Av, lying back in the front row with his feet up, eyes almost closed, as they gave their seminar, but very much awake, as question time revealed.…”