I have heard about human anti-mouse antibodies (HAMAs) and read that HAMAs neutralize murine antibodies, therefore decreasing the effectiveness of those murine antibodies. Is this true that HAMAs neutralize the murine antibodies? How?
It's common for the human immune system to create antibodies against many proteins, even some human proteins. Hemophiliacs who receive regular doses of clotting factor proteins often develop neutralizing antibodies against the clotting factor proteins, even though they are a human protein1.
Therefore it's not surprising that antibodies would be developed against mouse antibodies. There are differences between mouse and human antibodies, and human antibodies may bind to these different regions. I found the amino acid sequences for human2 and mouse3 immunoglobulin gamma heavy chain constant region and aligned them by hand and marked the matching amino acids:
Human: MELGLSWVFLVAILEGVQCEVQLVESGGGLVQPGGSLRLSCAASGFTFSSYWMSWVRQAPGKGLEWVANIKQDGSEKYYVDSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARECDNWF DPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHT CPPC PAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | | |||| || |||||||||||||||| |||| ||||||||||| | | |||||| ||||||| | || | |||||||||||||| | || ||| |||| |||||| | ||||| ||||| | ||| |||| | | |||||| |||| ||| |||| | | |||||| ||| ||| || |||||| || | | | | | |||| || | |||| ||| | |||||| ||| || |||| || ||||||||| || | | | |||| | | | |||| |||| | |||| ||| |||| || || ||| |||| || | |||| ||| | ||||||| || | || ||| || | ||| | |||||||| | |||| | | ||| | || | | | | | |||| Mouse: MDSRLNLVFLVLILKGVQCEVQLVESGGGLVKPGGSRKLSCAASGFTFSDYGMHWVRQAPEKGLEWVAYINSGSTTIYYADTVKGRFTISRDNAKNTLFLQMTSLRSEDTAMYYCARELWLRRIDYWGQGTTITVSSAKTTPPSVYPLAPGCGDTTGSSVTLGCLVKGYFPESVTVTWNSGSLSSSVHTFPALLQS GLYTMSSSVTVPSSTWPSQTVTCSVAHPASSTTVDKKLEPSGPISTINPCPPCKECHKCPAPNLEGGPSVFIFPPNIKDVLMISLTPKVTCVVVDVSEDDPDVQISWFVNNVEVHTAQTQTHREDYNSTIRVVSALPIQHQDWMSGKEFKCKVNNKDLPSPIERTISKIKGLVRAPQVYILPPPAEQLSRKDVSLTCLVVGFNPGDISVEWTSNGHTEENYKDTAPVLDSDGSYFIYSKLDIKTSKWEKTDSFSCNVRHEGLKNYYLKKTISRSPGK
As you can see, there are a lot of matching residues, but several differences. Keep in mind that antibodies also contain light chains, and that there are several other types of antibodies, I just used the IgG heavy chain as an example.
As mentioned in the comment, all antibodies have constant regions and variable regions. The variable regions are the binding sites on the ends of the two arms, and the constant regions are the rest of the molecule. When humans are injected with murine antibodies, the immune system recognises and sets up an immune response to them, through generation of HAMA. This affects the efficacy of the antibody because it is attacked the same way a pathogenic substance would be. Antibodies have different effects, but the most important one in this instance is through opsonisation (http://en.wikipedia.org/wiki/Opsonin#Examples). Because antibodies have two arms, they can bind multiple targets and cause a grouping and clumping. This also causes activation and phagocytosis through phagocytes (generally macrophages) which will ingest and destroy the therapeutic antibodies.
Antibodies that are mostly human with just mouse variable regions have been created to try and counter this problem, known as chimeric antibodies. Humanised antibodies are also available, which are entirely human with only the very tips of the variable regions (known as the hypervariable regions) are from mice. This reduces the problem as far as possible (http://en.wikipedia.org/wiki/Fusion_protein#Chimeric_protein_drugs).