On the Specificity of Antibodies

Richards, Frederic M.; Konigsberg, William H.; Rosenstein, Robert W.; Várga, J.

doi:10.1126/science.46122

Cited by 206 publications

(60 citation statements)

References 40 publications

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“…The selection procedure which I placed on these cytotoxic T cells in culture is probably analogous to the experiments with thymus-independent cells performed by Richards et al (26). They immunized rabbits with hapten A and showed by isoelectric focusing that a small, specific fraction of the serum antibody to A could also bind hapten B.…”

mentioning

confidence: 89%

Killer cells reactive to altered-self antigens can also be alloreactive.

Bevan

1977

Proc. Natl. Acad. Sci. U.S.A.

141

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Murine cytotoxic thymus-derived lymphocytes immunized against cells bearing foreign minor histocompatibility antigens are specific for the immunizing minor antigens and for their own major H-2 antigens; they do not lyse target cells that bear the correct minor antigens plus a different H-2 haplotype. These are referred to as "altered-self" or "self-plus-X" killer cells. Alloreactive killer cells are those which respond to allogeneic cells expressing a foreign (non-self) H-2 haplotype. In this study, cytotoxic lymphocytes were immunized against minor histocompatibility differences in vivo and in vitro. These effector cells kiled the immunizing altered-self target very well and showed about 1% cross-reactive lysis of an allogeneic target differing from themselves only at H-2. These cross-reactive clones were then selected for by repeated in vitro stimulation with the cells bearing foreign H-2 such that an effector population was obtained which lysed both the altered-self and the alloreactive target with the same efficiency. Cold target competition experiments established that the same killer cell could lyse either target; however, it was not determined if a killer cell uses the same receptor to respond to altered-self antigens as it does to respond to foreign H-2 antigens.

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mentioning

confidence: 89%

Killer cells reactive to altered-self antigens can also be alloreactive.

Bevan

1977

Proc. Natl. Acad. Sci. U.S.A.

141

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“…The latter concept was discussed in detail by Richards et a1 (41). They studied protein 460, a mouse IgA myeloma protein which bound the haptens 2-DNP-lys and 2 methyl-1, 4 naphthoquinone (menadione).…”

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confidence: 99%

Characteristics of antinuclear antibodies in rheumatoid. arthritis

Aitcheson

Peebles

Joslin

et al. 1980

Arthritis & Rheumatism

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The immunologic specificities of antinuclear antibodies (ANA) in sera from 97 patients with rheumatoid arthritis (RA) were studied. The frequency of ANA detected by immunofluorescence with mouse kidney sections as substrate was 60% (59/97) compared to 13% (7/ 55) in controls. IgM ANA was positive in 41% (40/97) of RA sera, IgG ANA in 40% (39/97), and IgA ANA in 33% (32/97). Specificities of antibodies in the ANA positive sera were examined by radioimmunoassay for antibodies to DNA and by immunodiffusion for antibodies to Sm antigen, nuclear ribonucleoprotein, and the SS-A and SS-B nuclear antigens. Antibodies to these nuclear antigens were found infrequently (1.7% to 6.8%). Sera were further investigated for antibodies to histones by an immunofluorescent method previously described using acid-extracted and histone reconstituted tissue sections. Twenty-four percent of the ANA positive sera (14/55) reacted with a histone-dependent nuclear antigen. The relationship of rheumatoid factor to ANA was studied by isolating rheumatoid factors (RF) from aggregated IgG absorbant columns. Ten of 19 isolated RF showed ANA activity, which did not result from complexes of rheumatoid factor with IgG ANA since IgM rheumatoid factor, dissociated from IgG under acid con- ditions, continued to show ANA activity. In 8 of 16 RA sera tested, both ANA and rheumatoid factor activity could be inhibited by aggregated IgG. Five of the crossreacting rheumatoid factors reacted specifically with a histone-dependent antigen in the reconstitution assay. These findings show that approximately WO of rheumatoid factors possess cross-reactivity with nuclear components, and histones are involved in a significant number of these reactions.

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“…Stimulation with a given antigen elicits not only specific antibodies, but also a variety of other immunoglobulins (1)(2)(3)(4)(5)(6)(7). Some of these react with compounds totally unrelated to the immunogen (7)(8)(9). The mechanisms involved in this phenomenon are not understood, but it has been suggested that immunologic stimulation may be involved in the process of lymphocyte maturation (7).…”

mentioning

confidence: 99%

Protective effect of immunization with nonviral antigens against Friend leukemia virus in mice

Nahon-Merlin¹,

Lacour²,

Friend³

et al. 1979

Proc. Natl. Acad. Sci. U.S.A.

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DBA/2 mice immunized with poly(A)·poly(U) complexed with methylated bovine serum albumin and emulsified in Freund's complete adjuvant were protected against challenge with Friend leukemia virus. There was no correlation between the level of antibody to the immunogen in the prechallenge serum and induced resistance to the virus. Although prechallenge sera of mice given the same amount of the duplex in a single inoculum bound 9.7% of poly(A)·poly([ 3 H]U) input, as compared to 45.3% bound by the prechallenge sera of mice given the immunogen in divided doses, both groups of mice were equally resistant to infection. Immunization with two other nonviral agents, bovine serum albumin fraction V or dinitrophenylated keyhole limpet hemocyanin, induced the same level of protection. A sparing effect of approximately 10 1.5 in infectivity was afforded the immunized mice. Immunization with either poly(A)·poly(U) alone or with the carrier methylated bovine serum albumin was ineffective. In addition to antibodies to the respective immunogens, the prechallenge sera of the immunized mice also contained antibody to Friend leukemia virus gp71. The presence of such viral antibodies was not always related to resistance to infection by Friend virus. Some immunized mice that survived infection did not have gp71 antibody in their serum before challenge, and mice immunized with poly(A)·poly(U) alone were susceptible to infection, although their prechallenge sera contained antibody to gp71. The mechanism involved in the induction of resistance to infection is not known. The effect may be mediated through a modification of the expression of both endogenous and exogenous type C viruses and affect immunological mechanisms controlling cellular responses.

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On the Specificity of Antibodies

Cited by 206 publications

References 40 publications

Killer cells reactive to altered-self antigens can also be alloreactive.

Killer cells reactive to altered-self antigens can also be alloreactive.

Characteristics of antinuclear antibodies in rheumatoid. arthritis

Protective effect of immunization with nonviral antigens against Friend leukemia virus in mice

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