History of Immunoglobulin molecules


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Snapshots in the history of Immunoglobulin molecules

1939

gamma-Globulin

gamma-Globulin

Tiseluis and Kabat in 1939 showed that antibodies belong to the γ-globulin fraction of serum proteins

1959

Three Fractions

Three Fractions

Porter digested γ-globulins with papain, a proteolytic enzyme, and recovered 3 fractions: Fractions I and II of molecular weights between 50 and 55KDa retained the antigen binding capacity, whereas fraction III, of 80 KDa was crystalizable, and have a higher carbohydrate content (Porter RR, Biochem J. 73:119-127, 1959).

1961

Heavy and Light chains

Heavy and Light chains

Edelman and Poulik reported that rabbit 7S γ-globulins and human myeloma proteins reduced in strong urea solutions and alkylated, separated into heavy (H) and light (L) chains bound by disulfide bonds (Edelman GM and Poulik MD, J Exp Med. 113:861-884, 1961)

1963

Y Structure

Y Structure

Porter and colleagues proposed the basic Y structure of four polypeptide chains and 5 interchain disulfide bonds (Fleischman JB et al., Biochem J. 88:220-228, 1963)

1965

V and C Regions

V and C Regions

Dreyer and Bennett proposed that the V and C regions must be the products of different genes (Proc Nat Acad Sci USA 54: 864-869, 1965)

IgA

IgA

Tomasi and coworkers demonstrated that IgA present in saliva and colostrum is produced locally and secreted as a dimer or trimer by (Tomasi TB et al., J Exp Med 121:101-124, 1965) and Newcomb and coworkers demonstrated the existence of the secretory piece (Newcomb RW et al., J immunol 101:905-913, 1968).

1968

Lambda chain

Lambda chain

Hood and Ein confirmed that the Lambda chain is encoded by two separate genes that are expressed as a single polypeptide chain (Nature 220:764-767, 1968)

1969

Variable and Constant Regions

Variable and Constant Regions

Edelman and coworkers reported the first complete sequence of a γG immunoglobulin molecule and demonstrated the existence of variable (V) and constant (C) regions in the H and L chains (Edelman GM et al., Proc Nat Acad Sci USA 63:78-85, 1969)

1972

Nobel Prize – 1972

Nobel Prize – 1972

Edelman and Porter shared the Nobel Prize in Medicine in 1972 “for their discoveries concerning the chemical structure of antibodies”

Gerald M. Edelman – Facts. Nobelprize.org. Nobel Media AB 2014.
Rodney R. Porter – FactsNobelprize.org. Nobel Media AB 2014.

 

1974

Monomers

Monomers

Koshland and coworkers demonstrated that the monomers of the polymeric IgM and IgA are linked by the J chain in a clasp way (Halpern MS and Koshland ME. Nature 228:1276-1278, 1970; Chapuis RM, Koshland ME, Proc Nat Acad Sci 71:657-661, 1974)

3D Structure

3D Structure

Poljak and colleagues described the three-dimensional structure of IgG(l) myeloma protein (Poljak et al., Proc Nat Acad Sci 71. 3440-3444, 1974).

1975

Monoclonal antibodies

Monoclonal antibodies

Kohler and Milstein (Nature 256: 495-497, 1975) reported that the fusion of a myeloma cell with a spleen specific antibody-producing cell results in a hybridoma that produces monoclonal antibodies against the specific antigen. Continuous culture of cloned hybrid cells allows the production of large amounts of monoclonal antibodies against the desired antigen.

1979

Somatic Rearrangements

Somatic Rearrangements

In the late 1970s, Tonegawa and colleagues in a series of elegant experiments demonstrated that immunoglobulin V and C genes undergo somatic rearrangements to form the complete immunoglobulin gene (Hozumi N, Tonegawa S, Proc Nat Acad Sci 73: 3628- 3632, 1976; Brack C et al., Cell 15:1-14, 1978; Sakano et al., Nature 277:627-633, 1979; Sakano et al., Nature 280: 288-294, 1979; Tonegawa S. Nature 302:575, 1983)

1984

Nobel Prize – 1984

Nobel Prize – 1984

In 1984, Niels Jerne, Georges Kohler and Cesar Milstein were awarded with the Nobel Prize for their discovery of the hybridomas technology for the production of large amounts of monoclonal antibodies for experimental, analytical, diagnostic and therapeutic purposes.

Niels K. Jerne – Facts. Nobelprize.org. Nobel Media AB 2014.
Georges J.F. Köhler – FactsNobelprize.org. Nobel Media AB 2014.
César Milstein – FactsNobelprize.org. Nobel Media AB 2014.

1987

Nobel Prize – 1987

Nobel Prize – 1987

In 1987, Susumo Tonegawa was awarded with the Nobel Prize for his discoveries on the mechanisms of somatic rearrangement of the immunoglobulin genes.

Susumo Tonegawa – FactsNobelprize.org. Nobel Media AB 2014.

Acknowledgement
History kindly supplied by Dr Luis Garcia – Immunopaedia Steering Committee

Luis F García
Emeritus Professor
Grupo de Inmunología Celular e Inmunogenética
Universidad de Antioquia
Medellín, Colombia
IUIS Education Committee
Immunopaedia Steering Committee

 
 
 
 
 
 
International Union of Immunological SocietiesUniversity of South AfricaInstitute of Infectious Disease and Molecular MedicineScience Education PrizesElizabeth Glazer Pediatric Aids Foundation