Heterophile Antigen: Examples, Diagnostic Applications

Common antigens (or antigens of similar nature) that are possessed by a variety of phylogenetically unrelated species are known as heterophile antigens.

Antibodies induced by these antigens cross-react with individual heterophilic antigens, such antibodies are known as heterophile antibodies i.e. antibodies produced against an antigen of one species can react with the other and vice versa.

The term heterophile antibody applies to antibodies having the capacity to react with certain antigens, which are quite different from, and phylogenetically unrelated to the one which evoked antibody response.

Heterophile antigens are involved in the pathogenesis of certain diseases, such as infectious mononucleosis, rheumatic fever, glomerulonephritis, etc.

Antigen of Group A beta-hemolytic streptococci (Streptococcus pyogenes) and antigens of the human myocardium are heterophilic. So in rheumatic fever, antibodies against group A streptococcal cell walls cross-react with human cardiolipin antigens and thus damage human heart tissues.

Heterophile antigen

Forssman antigen is another example of heterophile antigen. It is a lipid carbohydrate complex (glycolipid) widely distributed in man, animals, birds, plants and bacteria. Forssman antigen was named after the Swedish pathologist John F. Forssman who reported, ‘antibodies produced in rabbits against organ homogenates from guinea pigs reacted with sheep erythrocytes, causing hemolysis’.

Diagnostic Applications of Heterophilic Test

Heterophilic antigens can be used in various serologic tests. Antibody against one antigen can be detected in the patient’s serum by employing a different antigen which is heterophile (cross-reactive) to the first antigen.

  • Weil-Felix reaction: Used for the diagnosis of typhus fever.  Antibodies produced against Rickettsial antigens are detected by using cross-reacting Proteus antigen.
  • Paul-Bunnell test (Monospot test):  It is a rapid test for the diagnosis of infectious mononucleosis (a disease caused by the Epstein-Barr virus). In this test, sheep red blood cell antigens are used to detect cross-reacting antibodies in patient’s sera. Heterophile antibodies if present agglutinate sheep erythrocytes.
  • Cold agglutinin test: Patient suffering from primary atypical pneumonia caused by Mycoplasma pneumoniae produces antibodies that cross-reacts with human O blood group RBC. Agglutination of human O group erythrocytes at 4‎°C by the sera of suspected patient sample confirms the diagnosis.  Alternatively in Streptococcus MG test, such antibodies are detected using Streptococcus MG antigens. 


  1. Votava, M., Bartosová, D., Krchnáková, A., Crhová, K., & Kubinová, L. (1996). Diagnostic importance of heterophile antibodies and immunoglobulins IgA, IgE, IgM and low-avidity IgG against Epstein-Barr virus capsid antigen in children. Acta virologica, 40(2), 99–101. 
  2. Niculescu, F., Rus, H. G., Maican, A., & Petcovici, M. (1989). Anticorpii heterofili [Heterophile antibodies]. Revista de igiena, bacteriologie, virusologie, parazitologie, epidemiologie, pneumoftiziologie. Bacteriologia, virusologia, parazitologia, epidemiologia, 34(2), 107–112. 

Acharya Tankeshwar

Hello, thank you for visiting my blog. I am Tankeshwar Acharya. Blogging is my passion. As an asst. professor, I am teaching microbiology and immunology to medical and nursing students at PAHS, Nepal. I have been working as a microbiologist at Patan hospital for more than 10 years.

2 thoughts on “Heterophile Antigen: Examples, Diagnostic Applications

  1. Thanks for taking the time to post this data. I am recently one of your most passoniate followers. I have your RSS feed in my iphone and will check back regularly.

We love to get your feedback. Share your queries or comments

This site uses Akismet to reduce spam. Learn how your comment data is processed.

Recent Posts